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Cancers
Special Issues
Immunotherapy for Solid Tumors
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Immunotherapy for Solid Tumors

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (15 July 2022) | Viewed by 14398

Special Issue Editor

Dr. Elizabeth Fabre

E-Mail Website
Guest Editor
1. Department of Thoracic Oncology, Hôpital Européen Georges Pompidou, AP-HP, Carpem Cancer Institute, 75015 Paris, France
2. INSERM Team UMR_S970, Immunotherapy and Antiangiogenic Treatment in Cancerology, Paris Descartes University, 75015 Paris, France
Interests: biomarkers of resistance; immune checkpoint inhibitors; lung cancer; resident memory T cells; vaccination
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Immune checkpoint inhibitors (ICI), including those targeting the programmed cell death 1/programmed cell death ligand 1 (anti-PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4), represent a major breakthrough in the treatment of solid tumors. However, a majority of patients will still not respond to ICI, displaying primary resistance.

Therefore, the development of new combinations is required in order to improve efficacy using immuno-modulation.

Nevertheless, personalized treatments are needed and, thereby, a better understanding of the mechanisms of resistance and the relationship between tumor cells and microenvironment.

In addition, checkpoint inhibitors raise numerous questions regarding the response assessment, and the most relevant endpoints in clinical trials.

This Special Issue will highlight current challenges and new potential approaches to better predict, diagnose and overcome resistances in order to rationalize immunotherapy strategies. 

Dr. Elizabeth Fabre
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • immune-checkpoint inhibitors
  • immunotherapy, CTLA-4
  • PD-1
  • PD-L1
  • predictive biomarker
  • response evaluation
  • hyperprogression
  • pseudoprogression
  • immune related adverse events
  • immune checkpoint blockade resistance
  • immunomodulation
  • combination strategy

Published Papers (6 papers)

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Editorial

Jump to: Research, Review, Other

2 pages, 183 KiB  
Editorial
Immunotherapy for Solid Tumors
by Hortense de Saint Basile, Zineb Maaradji and Elizabeth Fabre
Cancers 2023, 15(6), 1646; https://doi.org/10.3390/cancers15061646 - 08 Mar 2023
Viewed by 1114
Abstract
The development of immune checkpoint inhibitors (ICIs) constitutes a major therapeutic advance in the treatment of a number of malignancies [...] Full article
(This article belongs to the Special Issue Immunotherapy for Solid Tumors)

Research

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20 pages, 9954 KiB  
Article
Dissecting the Immunological Profiles in NSD3-Amplified LUSC through Integrative Multi-Scale Analyses
by Duo Xu, Shengchen Liu, Xi Wu, Thomas M. Marti, Patrick Dorn, Ralph A. Schmid, Ren-Wang Peng and Yongqian Shu
Cancers 2022, 14(20), 4997; https://doi.org/10.3390/cancers14204997 - 12 Oct 2022
Cited by 3 | Viewed by 1816
Abstract
The histone H3 lysine 36 (H3K36) methyltransferase NSD3, a neighboring gene of FGFR1, has been identified as a critical genetic driver of lung squamous cell carcinoma (LUSC). However, the molecular characteristics, especially the immunological roles of NSD3 in driving carcinogenesis, are [...] Read more.
The histone H3 lysine 36 (H3K36) methyltransferase NSD3, a neighboring gene of FGFR1, has been identified as a critical genetic driver of lung squamous cell carcinoma (LUSC). However, the molecular characteristics, especially the immunological roles of NSD3 in driving carcinogenesis, are poorly understood. In this study, we systematically integrated multi-omics data (e.g., genome, transcriptome, proteome, and TMA array) to dissect the immunological profiles in NSD3-amplified LUSC. Next, pharmaco-transcriptomic correlation analysis was implemented to identify the molecular underpinnings and therapeutic vulnerabilities in LUSC. We revealed that NSD3-amplified LUSC presents a non-inflamed tumor immune microenvironment (TIME) state in multiple independent LUSC patient cohorts. Predictably, elevated NSD3 expression was correlated with a worse immunotherapy outcome. Further molecular characterizations revealed that the high activity of unfolded protein response (UPR) signaling might be a pivotal mediator for the non-immunogenic phenotype of NSD3-amplified LUSC. Concordantly, we showed that NSD3-amplified LUSCs exhibited a more sensitive phenotype to compounds targeting UPR branches than the wild-type group. In brief, our multi-level analyses point to a previously unappreciated immunological role for NSD3 and provide therapeutic rationales for NSD3-amplified squamous lung cancer. Full article
(This article belongs to the Special Issue Immunotherapy for Solid Tumors)
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15 pages, 2247 KiB  
Article
Grade 3–4 Immune-Related Adverse Events Induced by Immune Checkpoint Inhibitors in Non-Small-Cell Lung Cancer (NSCLC) Patients Are Correlated with Better Outcome: A Real-Life Observational Study
by Nadia Guezour, Ghassen Soussi, Solenn Brosseau, Baptiste Abbar, Charles Naltet, Charles Vauchier, Nicolas Poté, Lorry Hachon, Céline Namour, Antoine Khalil, Jean Trédaniel, Gérard Zalcman and Valérie Gounant
Cancers 2022, 14(16), 3878; https://doi.org/10.3390/cancers14163878 - 11 Aug 2022
Cited by 8 | Viewed by 1850
Abstract
Background: Immune checkpoint inhibitors (ICIs) have been a major advance in treating non-small-cell lung cancer (NSCLC). Programmed cell death protein-1/programmed death-ligand 1 blockade enhances immune function, mediating anti-tumor activity, yet causing immune-related adverse events (irAEs). We investigated the prognostic role of Grade 3–4 [...] Read more.
Background: Immune checkpoint inhibitors (ICIs) have been a major advance in treating non-small-cell lung cancer (NSCLC). Programmed cell death protein-1/programmed death-ligand 1 blockade enhances immune function, mediating anti-tumor activity, yet causing immune-related adverse events (irAEs). We investigated the prognostic role of Grade 3–4 irAEs on overall survival (OS). Methods: This observational study recruited advanced NSCLC patients who received ICIs at Bichat-Claude Bernard University Hospital and in a community hospital, Saint-Joseph Foundation (Paris), between 1 January 2016 and 31 December 2019. Immunotherapy as a single-agent or double-drug combination was applied in the first and later lines. Univariable and multivariable analyses were instrumental in evaluating the prognostic impact of irAEs. Results: Overall, 201 consecutive ICI-treated patients were enrolled. High-grade irAEs (Grades 3–4) occurred in 36 patients (17.9%), including 11 (30.5%) cases of pneumonitis, 8 (22.2%) of colitis, 4 (11.1%) hepatic, 3 (8.3%) dermatological, 2 (5.5%) neurological events, and 2 cases (5.5%) of poly-arthralgia. The median OS was 10.4 ± 1.36 months (95% CI:7.7–13.1), being significantly higher in patients with high-grade irAEs than those without, 27.8 months vs. 8.1 months, respectively (HR = 2.5; p < 0.0001). Multivariable analysis revealed an independent association between high-grade irAEs and longer OS (HR = 0.29, 95% CI: 0.2–0.6, p < 0.0001). Conclusions: Our real-life study confirms that high-grade irAEs predict longer OS in advanced NSCLC. Full article
(This article belongs to the Special Issue Immunotherapy for Solid Tumors)
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17 pages, 4258 KiB  
Article
GPR64, Screened from Ewing Sarcoma Cells, Is a Potential Target for Antibody-Based Therapy for Various Sarcomas
by Koichi Nakamura, Kunihiro Asanuma, Takayuki Okamoto, Keisuke Yoshida, Yumi Matsuyama, Kouji Kita, Tomohito Hagi, Tomoki Nakamura and Akihiro Sudo
Cancers 2022, 14(3), 814; https://doi.org/10.3390/cancers14030814 - 05 Feb 2022
Cited by 5 | Viewed by 2400
Abstract
Ewing sarcoma is an aggressive and the second most common bone tumor in adolescent and young adult patients. The 5-year survival rate is 60–70% for localized disease but 30% for patients with metastases. Here, we aimed to identify a therapeutic target for Ewing [...] Read more.
Ewing sarcoma is an aggressive and the second most common bone tumor in adolescent and young adult patients. The 5-year survival rate is 60–70% for localized disease but 30% for patients with metastases. Here, we aimed to identify a therapeutic target for Ewing sarcoma and evaluate antibody-based therapeutic agents using in vitro and in vivo models. We identified G protein-coupled receptor 64 (GPR64) as a therapeutic target for Ewing sarcoma via next-generation RNA-sequencing. GPR64v205 mRNA was expressed in HTB166, A673, MG63, 143B, HS-Sy II, and HT1080 cell lines as well as in Ewing sarcoma, undifferentiated pleomorphic sarcoma, leiomyosarcoma, dedifferentiated liposarcoma, and synovial sarcoma tissues. GPR64 expression was observed in 62.5% of sarcoma cases and was overexpressed in 33.9% cases. GPR64-specific monoclonal antibodies were tested as near-infrared probes for in vivo imaging using subcutaneous tumor mouse xenografts. Fluorescence intensity was stronger for the AF700-labeled anti-GPR64 antibody than that for the AF700-labeled isotype control antibody. GPR64 was detected in engrafted tumors of A673, 143B, HT1080, and the epididymis but not in other resected tissues. The anti-GPR64 antibody showed excellent binding to GPR64-positive tumors but not to healthy tissues. This antibody has potential for drug delivery in the antibody-based treatment of sarcomas. Full article
(This article belongs to the Special Issue Immunotherapy for Solid Tumors)
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Review

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41 pages, 1922 KiB  
Review
Immunomodulatory Properties of Immune Checkpoint Inhibitors—More than Boosting T-Cell Responses?
by Michael Kuske, Maximilian Haist, Thomas Jung, Stephan Grabbe and Matthias Bros
Cancers 2022, 14(7), 1710; https://doi.org/10.3390/cancers14071710 - 28 Mar 2022
Cited by 13 | Viewed by 3467
Abstract
The approval of immune checkpoint inhibitors (ICI) that serve to enhance effector T-cell anti-tumor responses has strongly improved success rates in the treatment of metastatic melanoma and other tumor types. The currently approved ICI constitute monoclonal antibodies blocking cytotoxic T-lymphocyte-associated protein (CTLA)-4 and [...] Read more.
The approval of immune checkpoint inhibitors (ICI) that serve to enhance effector T-cell anti-tumor responses has strongly improved success rates in the treatment of metastatic melanoma and other tumor types. The currently approved ICI constitute monoclonal antibodies blocking cytotoxic T-lymphocyte-associated protein (CTLA)-4 and anti-programmed cell death (PD)-1. By this, the T-cell-inhibitory CTLA-4/CD80/86 and PD-1/PD-1L/2L signaling axes are inhibited. This leads to sustained effector T-cell activity and circumvents the immune evasion of tumor cells, which frequently upregulate PD-L1 expression and modulate immune checkpoint molecule expression on leukocytes. As a result, profound clinical responses are observed in 40–60% of metastatic melanoma patients. Despite the pivotal role of T effector cells for triggering anti-tumor immunity, mounting evidence indicates that ICI efficacy may also be attributable to other cell types than T effector cells. In particular, emerging research has shown that ICI also impacts innate immune cells, such as myeloid cells, natural killer cells and innate lymphoid cells, which may amplify tumoricidal functions beyond triggering T effector cells, and thus improves clinical efficacy. Effects of ICI on non-T cells may additionally explain, in part, the character and extent of adverse effects associated with treatment. Deeper knowledge of these effects is required to further develop ICI treatment in terms of responsiveness of patients to treatment, to overcome resistance to ICI and to alleviate adverse effects. In this review we give an overview into the currently known immunomodulatory effects of ICI treatment in immune cell types other than the T cell compartment. Full article
(This article belongs to the Special Issue Immunotherapy for Solid Tumors)
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Other

12 pages, 1540 KiB  
Systematic Review
Impact of Proton Pump Inhibitors and Histamine-2-Receptor Antagonists on Non-Small Cell Lung Cancer Immunotherapy: A Systematic Review and Meta-Analysis
by Alessandro Rizzo, Antonio Cusmai, Francesco Giovannelli, Silvana Acquafredda, Lucia Rinaldi, Andrea Misino, Elisabetta Sara Montagna, Valentina Ungaro, Mariagrazia Lorusso and Gennaro Palmiotti
Cancers 2022, 14(6), 1404; https://doi.org/10.3390/cancers14061404 - 09 Mar 2022
Cited by 75 | Viewed by 3216
Abstract
(1) Background: In recent years, immunotherapy has revolutionized the treatment landscape of non-small cell lung cancer (NSCLC), representing a therapeutic breakthrough in this field. Antacid agents such as proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs) are commonly prescribed for extended periods in [...] Read more.
(1) Background: In recent years, immunotherapy has revolutionized the treatment landscape of non-small cell lung cancer (NSCLC), representing a therapeutic breakthrough in this field. Antacid agents such as proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs) are commonly prescribed for extended periods in NSCLC patients, and these drugs have the potential to modify the efficacy of immune checkpoint inhibitors (ICIs). (2) Materials and Methods: Herein, we conducted a systematic review and meta-analysis to investigate the impact of PPIs and H2RAs on progression-free survival (PFS) and overall survival (OS) among patients receiving immunotherapy for metastatic NSCLC. Effect measures for OS were Hazard Ratios (HRs) and 95% Confidence Intervals (CIs), which were extracted from available studies. Forest plots were used to assess HRs to describe the relationship between treatment and OS in the specified cohorts of patients. (3) Results: Six studies were included in the analysis, involving 2267 patients. The pooled HRs for OS and PFS were 1.4 (95% CI, 1.25–1.58) and 1.29 (95% CI, 1.17–1.43), respectively, suggesting that PPIs and H2RAs administration was negatively associated with PFS and OS. (4) Conclusion: Concomitant antacid use could modify the activity of ICIs in NSCLC patients. Full article
(This article belongs to the Special Issue Immunotherapy for Solid Tumors)
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