Editorial

2 pages, 170 KiB

Open AccessEditorial

Why Target Innate Immune Cells in Cancers?

by Mary Poupot

Cancers 2021, 13(4), 690; https://doi.org/10.3390/cancers13040690 - 09 Feb 2021

Cited by 2 | Viewed by 1235

The immune system is a smart way to fight cancer, with its precise targeting of cancer cells sparing healthy cells [...] Full article

(This article belongs to the Special Issue Targeting the Innate Immune Cells in Cancers)

Research

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18 pages, 4362 KiB

Open AccessArticle

CD47-SIRPα Checkpoint Disruption in Metastases Requires Tumor-Targeting Antibody for Molecular and Engineered Macrophage Therapies

by Jason C. Andrechak, Lawrence J. Dooling, Michael P. Tobin, William Zhang, Brandon H. Hayes, Justine Y. Lee, Xiaoling Jin, Jerome Irianto and Dennis E. Discher

Cancers 2022, 14(8), 1930; https://doi.org/10.3390/cancers14081930 - 11 Apr 2022

Cited by 4 | Viewed by 4052

Abstract

The macrophage checkpoint interaction CD47-SIRPα is an emerging target for cancer therapy, but clinical trials of monoclonal anti-CD47 show efficacy only in liquid tumors when combined with tumor-opsonizing IgG. Here, in challenging metastatic solid tumors, CD47 deletion shows no effect on tumor growth [...] Read more.

The macrophage checkpoint interaction CD47-SIRPα is an emerging target for cancer therapy, but clinical trials of monoclonal anti-CD47 show efficacy only in liquid tumors when combined with tumor-opsonizing IgG. Here, in challenging metastatic solid tumors, CD47 deletion shows no effect on tumor growth unless combined with otherwise ineffective tumor-opsonization, and we likewise show wild-type metastases are suppressed by SIRPα-blocked macrophages plus tumor-opsonization. Lung tumor nodules of syngeneic B16F10 melanoma cells with CD47 deletion show opsonization drives macrophage phagocytosis of B16F10s, consistent with growth versus phagocytosis calculus for exponential suppression of cancer. Wild-type CD47 levels on metastases in lungs of immunocompetent mice and on human metastases in livers of immunodeficient mice show that systemic injection of antibody-engineered macrophages also suppresses growth. Such in vivo functionality can be modulated by particle pre-loading of the macrophages. Thus, even though CD47-SIRPα disruption and tumor-opsonizing IgG are separately ineffective against established metastatic solid tumors, their combination in molecular and cellular therapies prolongs survival. Full article

(This article belongs to the Special Issue Targeting the Innate Immune Cells in Cancers)

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15 pages, 15858 KiB

Open AccessArticle

IL-10 Rescues CLL Survival through Repolarization of Inflammatory Nurse-like Cells

by Marcin Domagala, Loïc Ysebaert, Laetitia Ligat, Frederic Lopez, Jean-Jacques Fournié, Camille Laurent and Mary Poupot

Cancers 2022, 14(1), 16; https://doi.org/10.3390/cancers14010016 - 21 Dec 2021

Cited by 10 | Viewed by 2532

Abstract

Tumor-associated macrophages (TAMs) in chronic lymphocytic leukemia (CLL) are also called nurse-like cells (NLC), and confer survival signals through the release of soluble factors and cellular contacts. While in most patient samples the presence of NLC in co-cultures guarantees high viability of leukemic [...] Read more.

Tumor-associated macrophages (TAMs) in chronic lymphocytic leukemia (CLL) are also called nurse-like cells (NLC), and confer survival signals through the release of soluble factors and cellular contacts. While in most patient samples the presence of NLC in co-cultures guarantees high viability of leukemic cells in vitro, in some cases this protective effect is absent. These macrophages are characterized by an “M1-like phenotype”. We show here that their reprogramming towards an M2-like phenotype (tumor-supportive) with IL-10 leads to an increase in leukemic cell survival. Inflammatory cytokines, such as TNF, are also able to depolarize M2-type protective NLC (decreasing CLL cell viability), an effect which is countered by IL-10 or blocking antibodies. Interestingly, both IL-10 and TNF are implied in the pathophysiology of CLL and their elevated level is associated with bad prognosis. We propose that the molecular balance between these two cytokines in CLL niches plays an important role in the maintenance of the protective phenotype of NLCs, and therefore in the survival of CLL cells. Full article

(This article belongs to the Special Issue Targeting the Innate Immune Cells in Cancers)

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17 pages, 2563 KiB

Open AccessArticle

Targeting Cross-Presentation as a Route to Improve the Efficiency of Peptide-Based Cancer Vaccines

by Ben Wylie, Ferrer Ong, Hanane Belhoul-Fakir, Kristin Priebatsch, Heique Bogdawa, Anja Stirnweiss, Paul Watt, Paula Cunningham, Shane R. Stone and Jason Waithman

Cancers 2021, 13(24), 6189; https://doi.org/10.3390/cancers13246189 - 08 Dec 2021

Cited by 7 | Viewed by 3138

Abstract

Cross-presenting dendritic cells (DC) offer an attractive target for vaccination due to their unique ability to process exogenous antigens for presentation on MHC class I molecules. Recent reports have established that these DC express unique surface receptors and play a critical role in [...] Read more.

Cross-presenting dendritic cells (DC) offer an attractive target for vaccination due to their unique ability to process exogenous antigens for presentation on MHC class I molecules. Recent reports have established that these DC express unique surface receptors and play a critical role in the initiation of anti-tumor immunity, opening the way for the development of vaccination strategies specifically targeting these cells. This study investigated whether targeting cross-presenting DC by two complementary mechanisms could improve vaccine effectiveness, in both a viral setting and in a murine melanoma model. Our novel vaccine construct contained the XCL1 ligand, to target uptake to XCR1⁺ cross-presenting DC, and a cell penetrating peptide (CPP) with endosomal escape properties, to enhance antigen delivery into the cross-presentation pathway. Using a prime-boost regimen, we demonstrated robust expansion of antigen-specific T cells following vaccination with our CPP-linked peptide vaccine and protective immunity against HSV-1 skin infection, where vaccine epitopes were natively expressed by the virus. Additionally, our novel vaccination strategy slowed tumor outgrowth in a B16 murine melanoma model, compared to adjuvant only controls, suggesting antigen-specific anti-tumor immunity was generated following vaccination. These findings suggest that novel strategies to target the antigen cross-presentation pathway in DC may be beneficial for the generation of anti-tumor immunity. Full article

(This article belongs to the Special Issue Targeting the Innate Immune Cells in Cancers)

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21 pages, 5809 KiB

Open AccessArticle

Enhancing Therapeutic Efficacy of Double Negative T Cells against Acute Myeloid Leukemia Using Idelalisib

by Hyeonjeong Kang, Jong Bok Lee, Ismat Khatri, Yoosu Na, Cheryl D’Souza, Andrea Arruda, Mark D. Minden and Li Zhang

Cancers 2021, 13(20), 5039; https://doi.org/10.3390/cancers13205039 - 09 Oct 2021

Cited by 5 | Viewed by 2212

Abstract

The double negative T cell (DNT) is a unique subset of T cells with potent anti-leukemic potential. Previously, DNT therapy has been shown to effectively target AML cells in patient-derived xenograft (PDX) models. Further, a recently completed phase I/IIa clinical study demonstrated the [...] Read more.

The double negative T cell (DNT) is a unique subset of T cells with potent anti-leukemic potential. Previously, DNT therapy has been shown to effectively target AML cells in patient-derived xenograft (PDX) models. Further, a recently completed phase I/IIa clinical study demonstrated the safety, feasibility, and potential efficacy in AML patients that relapsed after allogeneic hematopoietic stem cell transplantation. However, the persistence and durability of DNT-mediated anti-leukemic response is less well understood. In this study, we characterized the in vivo persistence of DNTs in PDX models. Further, we improved the efficacy and durability of DNT-mediated activity with phosphoinositide 3-kinase delta (PI3Kδ) inhibition. Mechanistically, DNTs treated with the PI3Kδ inhibitor, Idelalisib (Ide), exhibited early memory phenotype with superior viability and proliferative capacity but less cell exhaustion. Collectively, the findings from this study support the use of Ide-treated DNTs to improve its therapeutic outcome. Full article

(This article belongs to the Special Issue Targeting the Innate Immune Cells in Cancers)

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11 pages, 3463 KiB

Open AccessArticle

Effect of Vitamin D Supplements on Relapse of Digestive Tract Cancer with Tumor Stromal Immune Response: A Secondary Analysis of the AMATERASU Randomized Clinical Trial

by Taisuke Akutsu, Kazuki Kanno, Shinya Okada, Hironori Ohdaira, Yutaka Suzuki and Mitsuyoshi Urashima

Cancers 2021, 13(18), 4708; https://doi.org/10.3390/cancers13184708 - 20 Sep 2021

Cited by 3 | Viewed by 2266

Abstract

The aim was to examine whether vitamin D supplementation (2000 IU/day) reduces the risk of relapse in a subgroup of patients with digestive tract cancer, showing a sufficient immune response in tumor stroma by conducting secondary subgroup analyses of the AMATERASU randomized, double-blind, [...] Read more.

The aim was to examine whether vitamin D supplementation (2000 IU/day) reduces the risk of relapse in a subgroup of patients with digestive tract cancer, showing a sufficient immune response in tumor stroma by conducting secondary subgroup analyses of the AMATERASU randomized, double-blind, placebo-controlled trial (UMIN000001977). A total of 372 patients were divided into two subgroups stratified by the median density of immune cells infiltrating in tumor stroma into higher and lower halves. In the higher-half subgroup of CD56+ cells, the relapse ratio was significantly lower in the vitamin D group (7.4%) than in the placebo group (20.5%) (subdistribution hazard ratio (SHR), 0.35; 95% confidence interval (CI), 0.15–0.82), but it was equivalent (25.2% vs. 22.7%) in the lower-half subgroup of CD56+ cells (SHR, 1.21; 95% CI, 0.68–2.19) with a significant interaction (P_interaction = 0.02). Although there were no significant differences, the risk of relapse was lower in the vitamin D group than in the placebo group in the higher half of CD45RO+ memory T cells (8.9% vs. 19.2%), and of CD8+ cytotoxic T cells (11.3% vs. 22.5%). In patients with digestive tract cancer, vitamin D supplementation was hypothesized to reduce the risk of relapse in the subgroup of patients who already have an adequate infiltration of immune cells in their tumor stroma. Full article

(This article belongs to the Special Issue Targeting the Innate Immune Cells in Cancers)

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18 pages, 4344 KiB

Open AccessArticle

Retargeting of NK-92 Cells against High-Risk Rhabdomyosarcomas by Means of an ERBB2 (HER2/Neu)-Specific Chimeric Antigen Receptor

by Leonie D. H. Gossel, Catrin Heim, Lisa-Marie Pfeffermann, Laura M. Moser, Halvard B. Bönig, Thomas E. Klingebiel, Peter Bader, Winfried S. Wels, Michael Merker and Eva Rettinger

Cancers 2021, 13(6), 1443; https://doi.org/10.3390/cancers13061443 - 22 Mar 2021

Cited by 7 | Viewed by 2663

Abstract

The dismal prognosis of pediatric and young adult patients with high-risk rhabdomyosarcoma (RMS) underscores the need for novel treatment options for this patient group. In previous studies, the tumor-associated surface antigen ERBB2 (HER2/neu) was identified as targetable in high-risk RMS. As a proof [...] Read more.

The dismal prognosis of pediatric and young adult patients with high-risk rhabdomyosarcoma (RMS) underscores the need for novel treatment options for this patient group. In previous studies, the tumor-associated surface antigen ERBB2 (HER2/neu) was identified as targetable in high-risk RMS. As a proof of concept, in this study, a novel treatment approach against RMS tumors using a genetically modified natural killer (NK)-92 cell line (NK-92/5.28.z) as an off-the-shelf ERBB2-chimeric antigen receptor (CAR)-engineered cell product was preclinically explored. In cytotoxicity assays, NK-92/5.28.z cells specifically recognized and efficiently eliminated RMS cell suspensions, tumor cell monolayers, and 3D tumor spheroids via the ERBB2-CAR even at effector-to-target ratios as low as 1:1. In contrast to unmodified parental NK-92 cells, which failed to lyse RMS cells, NK-92/5.28.z cells proliferated and became further activated through contact with ERBB2-positive tumor cells. Furthermore, high amounts of effector molecules, such as proinflammatory and antitumoral cytokines, were found in cocultures of NK-92/5.28.z cells with tumor cells. Taken together, our data suggest the enormous potential of this approach for improving the immunotherapy of treatment-resistant tumors, revealing the dual role of NK-92/5.28.z cells as CAR-targeted killers and modulators of endogenous adaptive immunity even in the inhibitory tumor microenvironment of high-risk RMS. Full article

(This article belongs to the Special Issue Targeting the Innate Immune Cells in Cancers)

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Review

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40 pages, 3174 KiB

Open AccessReview

Evolution and Targeting of Myeloid Suppressor Cells in Cancer: A Translational Perspective

by Augusto Bleve, Francesca Maria Consonni, Chiara Porta, Valentina Garlatti and Antonio Sica

Cancers 2022, 14(3), 510; https://doi.org/10.3390/cancers14030510 - 20 Jan 2022

Cited by 6 | Viewed by 3624

Abstract

In recent years, the immune system has emerged as a critical regulator of tumor development, progression and dissemination. Advanced therapeutic approaches targeting immune cells are currently under clinical use and improvement for the treatment of patients affected by advanced malignancies. Among these, anti-PD1/PD-L1 [...] Read more.

In recent years, the immune system has emerged as a critical regulator of tumor development, progression and dissemination. Advanced therapeutic approaches targeting immune cells are currently under clinical use and improvement for the treatment of patients affected by advanced malignancies. Among these, anti-PD1/PD-L1 and anti-CTLA4 immune checkpoint inhibitors (ICIs) are the most effective immunotherapeutic drugs at present. In spite of these advances, great variability in responses to therapy exists among patients, probably due to the heterogeneity of both cancer cells and immune responses, which manifest in diverse forms in the tumor microenvironment (TME). The variability of the immune profile within TME and its prognostic significance largely depend on the frequency of the infiltrating myeloid cells, which often represent the predominant population, characterized by high phenotypic heterogeneity. The generation of heterogeneous myeloid populations endowed with tumor-promoting activities is typically promoted by growing tumors, indicating the sequential levels of myeloid reprogramming as possible antitumor targets. This work reviews the current knowledge on the events governing protumoral myelopoiesis, analyzing the mechanisms that drive the expansion of major myeloid subsets, as well as their functional properties, and highlighting recent translational strategies for clinical developments. Full article

(This article belongs to the Special Issue Targeting the Innate Immune Cells in Cancers)

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29 pages, 1685 KiB

Open AccessReview

Immune Checkpoints and Innate Lymphoid Cells—New Avenues for Cancer Immunotherapy

by Nicolas Jacquelot, Maryam Ghaedi, Kathrin Warner, Douglas C. Chung, Sarah Q. Crome and Pamela S. Ohashi

Cancers 2021, 13(23), 5967; https://doi.org/10.3390/cancers13235967 - 27 Nov 2021

Cited by 12 | Viewed by 3097

Abstract

Immune checkpoints (IC) are broadly characterized as inhibitory pathways that tightly regulate the activation of the immune system. These molecular “brakes” are centrally involved in the maintenance of immune self-tolerance and represent a key mechanism in avoiding autoimmunity and tissue destruction. Antibody-based therapies [...] Read more.

Immune checkpoints (IC) are broadly characterized as inhibitory pathways that tightly regulate the activation of the immune system. These molecular “brakes” are centrally involved in the maintenance of immune self-tolerance and represent a key mechanism in avoiding autoimmunity and tissue destruction. Antibody-based therapies target these inhibitory molecules on T cells to improve their cytotoxic function, with unprecedented clinical efficacies for a number of malignancies. Many of these ICs are also expressed on innate lymphoid cells (ILC), drawing interest from the field to understand their function, impact for anti-tumor immunity and potential for immunotherapy. In this review, we highlight ILC specificities at different tissue sites and their migration potential upon inflammatory challenge. We further summarize the current understanding of IC molecules on ILC and discuss potential strategies for ILC modulation as part of a greater anti-cancer armamentarium. Full article

(This article belongs to the Special Issue Targeting the Innate Immune Cells in Cancers)

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18 pages, 775 KiB

Open AccessReview

The Role of Innate Immune Cells in Tumor Invasion and Metastasis

by Yu-Kuan Huang, Rita A. Busuttil and Alex Boussioutas

Cancers 2021, 13(23), 5885; https://doi.org/10.3390/cancers13235885 - 23 Nov 2021

Cited by 7 | Viewed by 2999

Abstract

Metastasis is considered one of the hallmarks of cancer and enhanced tumor invasion and metastasis is significantly associated with cancer mortality. Metastasis occurs via a series of integrated processes involving tumor cells and the tumor microenvironment. The innate immune components of the microenvironment [...] Read more.

Metastasis is considered one of the hallmarks of cancer and enhanced tumor invasion and metastasis is significantly associated with cancer mortality. Metastasis occurs via a series of integrated processes involving tumor cells and the tumor microenvironment. The innate immune components of the microenvironment have been shown to engage with tumor cells and not only regulate their proliferation and survival, but also modulate the surrounding environment to enable cancer progression. In the era of immune therapies, it is critical to understand how different innate immune cell populations are involved in this process. This review summarizes recent literature describing the roles of innate immune cells during the tumor metastatic cascade. Full article

(This article belongs to the Special Issue Targeting the Innate Immune Cells in Cancers)

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19 pages, 2074 KiB

Open AccessReview

Kinase Inhibitors’ Effects on Innate Immunity in Solid Cancers

by Chunying Peng, Katrin Rabold, Willem J. M. Mulder, Martin Jaeger and Romana T. Netea-Maier

Cancers 2021, 13(22), 5695; https://doi.org/10.3390/cancers13225695 - 14 Nov 2021

Cited by 4 | Viewed by 2607

Abstract

Innate immune cells constitute a plastic and heterogeneous cell population of the tumor microenvironment. Because of their high tumor infiltration and close interaction with resident tumor cells, they are compelling targets for anti-cancer therapy through either ablation or functionally reprogramming. Kinase inhibitors (KIs) [...] Read more.

Innate immune cells constitute a plastic and heterogeneous cell population of the tumor microenvironment. Because of their high tumor infiltration and close interaction with resident tumor cells, they are compelling targets for anti-cancer therapy through either ablation or functionally reprogramming. Kinase inhibitors (KIs) that target aberrant signaling pathways in tumor proliferation and angiogenesis have been shown to have additional immunological effects on myeloid cells that may contribute to a protective antitumor immune response. However, in patients with malignancies, these effects are poorly described, warranting meticulous research to identify KIs’ optimal immunomodulatory effect to support developing targeted and more effective immunotherapy. As many of these KIs are currently in clinical trials awaiting approval for the treatment of several types of solid cancer, we evaluate here the information on this drug class’s immunological effects and how such mechanisms can be harnessed to improve combined treatment regimens in cancer. Full article

(This article belongs to the Special Issue Targeting the Innate Immune Cells in Cancers)

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22 pages, 15655 KiB

Open AccessReview

The Role of the Innate Immune System in Cancer Dormancy and Relapse

by Noah M. Chernosky and Ilaria Tamagno

Cancers 2021, 13(22), 5621; https://doi.org/10.3390/cancers13225621 - 10 Nov 2021

Cited by 13 | Viewed by 3634

Abstract

Metastatic spread and recurrence are intimately linked to therapy failure, which remains an overarching clinical challenge for patients with cancer. Cancer cells often disseminate early in the disease process and can remain dormant for years or decades before re-emerging as metastatic disease, often [...] Read more.

Metastatic spread and recurrence are intimately linked to therapy failure, which remains an overarching clinical challenge for patients with cancer. Cancer cells often disseminate early in the disease process and can remain dormant for years or decades before re-emerging as metastatic disease, often after successful treatment. The interactions of dormant cancer cells and their metastatic niche, comprised of various stromal and immune cells, can determine the length of time that cancer cells remain dormant, as well as when they reactivate. New studies are defining how innate immune cells in the primary tumor may be corrupted to help facilitate many aspects of dissemination and re-emergence from a dormant state. Although the scientific literature has partially shed light on the drivers of immune escape in cancer, the specific mechanisms regulating metastasis and dormancy in the context of anti-tumor immunity are still mostly unknown. This review follows the journey of metastatic cells from dissemination to dormancy and the onset of metastatic outgrowth and recurrent tumor development, with emphasis on the role of the innate immune system. To this end, further research identifying how immune cells interact with cancer cells at each step of cancer progression will pave the way for new therapies that target the reactivation of dormant cancer cells into recurrent, metastatic cancers. Full article

(This article belongs to the Special Issue Targeting the Innate Immune Cells in Cancers)

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20 pages, 847 KiB

Open AccessReview

The Growing Relevance of Immunoregulation in Pediatric Brain Tumors

by Viktoria Melcher and Kornelius Kerl

Cancers 2021, 13(22), 5601; https://doi.org/10.3390/cancers13225601 - 09 Nov 2021

Cited by 5 | Viewed by 2502

Abstract

Pediatric brain tumors are genetically heterogeneous solid neoplasms. With a prevailing poor prognosis and widespread resistance to conventional multimodal therapy, these aggressive tumors are the leading cause of childhood cancer-related deaths worldwide. Advancement in molecular research revealed their unique genetic and epigenetic characteristics [...] Read more.

Pediatric brain tumors are genetically heterogeneous solid neoplasms. With a prevailing poor prognosis and widespread resistance to conventional multimodal therapy, these aggressive tumors are the leading cause of childhood cancer-related deaths worldwide. Advancement in molecular research revealed their unique genetic and epigenetic characteristics and paved the way for more defined prognostication and targeted therapeutic approaches. Furthermore, uncovering the intratumoral metrics on a single-cell level placed non-malignant cell populations such as innate immune cells into the context of tumor manifestation and progression. Targeting immune cells in pediatric brain tumors entails unique challenges but promising opportunities to improve outcome. Herein, we outline the current understanding of the role of the immune regulation in pediatric brain tumors. Full article

(This article belongs to the Special Issue Targeting the Innate Immune Cells in Cancers)

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19 pages, 1105 KiB

Open AccessReview

Targeting Tumor-Associated Macrophages in Cancer Immunotherapy

by Amy J. Petty, Dwight H. Owen, Yiping Yang and Xiaopei Huang

Cancers 2021, 13(21), 5318; https://doi.org/10.3390/cancers13215318 - 22 Oct 2021

Cited by 24 | Viewed by 3465

Abstract

Tumor-associated macrophages (TAMs) represent the most abundant leukocyte population in most solid tumors and are greatly influenced by the tumor microenvironment. More importantly, these macrophages can promote tumor growth and metastasis through interactions with other cell populations within the tumor milieu and have [...] Read more.

Tumor-associated macrophages (TAMs) represent the most abundant leukocyte population in most solid tumors and are greatly influenced by the tumor microenvironment. More importantly, these macrophages can promote tumor growth and metastasis through interactions with other cell populations within the tumor milieu and have been associated with poor outcomes in multiple tumors. In this review, we examine how the tumor microenvironment facilitates the polarization of TAMs. Additionally, we evaluate the mechanisms by which TAMs promote tumor angiogenesis, induce tumor invasion and metastasis, enhance chemotherapeutic resistance, and foster immune evasion. Lastly, we focus on therapeutic strategies that target TAMs in the treatments of cancer, including reducing monocyte recruitment, depleting or reprogramming TAMs, and targeting inhibitory molecules to increase TAM-mediated phagocytosis. Full article

(This article belongs to the Special Issue Targeting the Innate Immune Cells in Cancers)

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20 pages, 1010 KiB

Open AccessReview

Therapeutic Potential of Innate Lymphoid Cells for Multiple Myeloma Therapy

by Aneta Szudy-Szczyrek, Sean Ahern, Magdalena Kozioł, Daria Majowicz, Michał Szczyrek, Janusz Krawczyk and Marek Hus

Cancers 2021, 13(19), 4806; https://doi.org/10.3390/cancers13194806 - 26 Sep 2021

Cited by 5 | Viewed by 2480

Abstract

Innate lymphoid cells (ILCs) are a recently identified family of lymphocyte-like cells lacking a specific antigen receptor. They are part of the innate immune system. They play a key role in tissue homeostasis and also control inflammatory and neoplastic processes. In response to [...] Read more.

Innate lymphoid cells (ILCs) are a recently identified family of lymphocyte-like cells lacking a specific antigen receptor. They are part of the innate immune system. They play a key role in tissue homeostasis and also control inflammatory and neoplastic processes. In response to environmental stimuli, ILCs change their phenotype and functions, and influence the activity of other cells in the microenvironment. ILC dysfunction can lead to a wide variety of diseases, including cancer. ILC can be divided into three subgroups: ILC Group 1, comprising NK cells and ILC1; Group 2, including ILC2 alone; and Group 3, containing Lymphoid Tissue inducers (LTi) and ILC3 cells. While Group 1 ILCs mainly exert antitumour activity, Group 2 and Group 3 ILCs are protumorigenic in nature. A growing body of preclinical and clinical data support the role of ILCs in the pathogenesis of multiple myeloma (MM). Therefore, targeting ILCs may be of clinical benefit. In this manuscript, we review the available data on the role of ILCs in MM immunology and therapy. Full article

(This article belongs to the Special Issue Targeting the Innate Immune Cells in Cancers)

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16 pages, 3188 KiB

Open AccessSystematic Review

The Prognostic Value of CD206 in Solid Malignancies: A Systematic Review and Meta-Analysis

by Jens M. Debacker, Odrade Gondry, Tony Lahoutte, Marleen Keyaerts and Wouter Huvenne

Cancers 2021, 13(14), 3422; https://doi.org/10.3390/cancers13143422 - 08 Jul 2021

Cited by 15 | Viewed by 3077

Abstract

An increased presence of CD206-expressing tumor associated macrophages in solid cancers was proposed to be associated with worse outcomes in multiple types of malignancies, but contradictory results are published. We performed a reproducible systematic review and meta-analysis to provide increased evidence to confirm [...] Read more.

An increased presence of CD206-expressing tumor associated macrophages in solid cancers was proposed to be associated with worse outcomes in multiple types of malignancies, but contradictory results are published. We performed a reproducible systematic review and meta-analysis to provide increased evidence to confirm or reject this hypothesis following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. The Embase, Web of Science, and MEDLINE-databases were systematically searched for eligible manuscripts. A total of 27 papers studying the prognostic impact of CD206 in 14 different tumor types were identified. Meta-analyses showed a significant impact on the overall survival (OS) and disease-free survival (DFS). While no significant differences were revealed in progression-free survival (PFS) and disease-specific survival (DSS), a shift towards negative survival was correlated with increased CD206-expresion. As a result of the different tumor types, large heterogeneity was present between the different tumor types. Subgroup analysis of hepatocellular carcinoma and gastric cancers revealed no heterogeneity, associated with a significant negative impact on OS in both groups. The current systematic review displays the increased presence CD206-expressing macrophages as a significant negative prognostic biomarker for both OS and DFS in patients diagnosed with solid cancers. Because a heterogenous group of tumor types was included in the meta-analysis, the results cannot be generalized. These results can, however, be used to further lead follow-up research to validate the specific prognostic value of CD206 in individual tumor types and therapeutic approaches. Full article

(This article belongs to the Special Issue Targeting the Innate Immune Cells in Cancers)

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