Editorial

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Open AccessEditorial

Significance of Tumor Microenvironment for Regulating Pancreatic Cancer

by Hideaki Ijichi

Cancers 2023, 15(9), 2482; https://doi.org/10.3390/cancers15092482 - 26 Apr 2023

Viewed by 958

Abstract

Pancreatic cancer is the most lethal common cancer in the world [...] Full article

(This article belongs to the Special Issue Tumor Microenvironment and Pancreatic Cancer)

Research

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14 pages, 3164 KiB

Open AccessArticle

Myofibroblastic CAF Density, Not Activated Stroma Index, Indicates Prognosis after Neoadjuvant Therapy of Pancreatic Carcinoma

by Ulrike Heger, Anna Martens, Lisa Schillings, Britta Walter, Domenic Hartmann, Ulf Hinz, Thomas Pausch, Nathalia Giese, Christoph W. Michalski and Thilo Hackert

Cancers 2022, 14(16), 3881; https://doi.org/10.3390/cancers14163881 - 11 Aug 2022

Cited by 5 | Viewed by 1881

Abstract

Neoadjuvant therapy (NT) for advanced PDAC is an emerging concept, affecting both stroma and tumor. The Activated Stroma Index (ASI; ratio of activated cancer-associated fibroblasts (CAF) to collagen deposition) is a prognostic marker in upfront resected pancreatic adenocarcinoma (PDAC). We assessed ASI and [...] Read more.

Neoadjuvant therapy (NT) for advanced PDAC is an emerging concept, affecting both stroma and tumor. The Activated Stroma Index (ASI; ratio of activated cancer-associated fibroblasts (CAF) to collagen deposition) is a prognostic marker in upfront resected pancreatic adenocarcinoma (PDAC). We assessed ASI and its prognostic relevance after NT. Tissue from resection specimens of n = 48 PDAC patients after neoadjuvant chemotherapy with FOLFIRINOX (FOL; n = 31), gemcitabine + nab-paclitaxel (GEM; 7) or combination treatment (COMB; 10) was compared with upfront resected matched controls (RES; 69). Activated CAFs were assessed by immunohistochemistry for α-SMA, and collagen was stained with aniline blue; the stained area was then determined by computational imaging analysis and ASI was calculated. In GEM, ASI was significantly higher and collagen deposition lower than in controls and FOL. The lowest quartile of ASI values had significantly longer overall survival (OS) in RES, whereas in FOL, the highest quartile had the best prognosis. After NT, OS was significantly improved in the α-SMA-high group; in RES, however, survival was independent of α-SMA. Reversed prognostic association of ASI thus points to the differing significance of stromal composition after FOL, while improved prognosis with high CAF abundance suggests a synergistic effect of myofibroblasts with chemotherapy. These divergences impede usability of ASI after NT. Full article

(This article belongs to the Special Issue Tumor Microenvironment and Pancreatic Cancer)

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20 pages, 1941 KiB

Open AccessArticle

Chemokine Receptor Expression on T Cells Is Modulated by CAFs and Chemokines Affect the Spatial Distribution of T Cells in Pancreatic Tumors

by Laia Gorchs, Marlies Oosthoek, Tülay Yucel-Lindberg, Carlos Fernández Moro and Helen Kaipe

Cancers 2022, 14(15), 3826; https://doi.org/10.3390/cancers14153826 - 06 Aug 2022

Cited by 8 | Viewed by 2468

Abstract

The accumulation of T cells is associated with a better prognosis in pancreatic cancer. However, the immunosuppressive tumor microenvironment, largely composed by cancer-associated fibroblasts (CAFs), can prevent T cells from reaching the tumor nests. We examined how human CAFs modulated chemokine receptors known [...] Read more.

The accumulation of T cells is associated with a better prognosis in pancreatic cancer. However, the immunosuppressive tumor microenvironment, largely composed by cancer-associated fibroblasts (CAFs), can prevent T cells from reaching the tumor nests. We examined how human CAFs modulated chemokine receptors known to be associated with T cell trafficking, CXCR3 and CCR5, and T cell exclusion, CXCR4. CAFs decreased the expression of CXCR3 and CCR5 but increased CXCR4 expression in both 2D and 3D cultures, affecting the migratory capacity of T cells towards CXCL10. An immunohistochemistry analysis showed that very few T cells were found in the tumor nests. Within the stroma, CD8⁺ T cells were localized more distantly from the malignant cells whereas CD4⁺ T cells were more equally distributed. Tumor tissues with a high production of chemokines were associated with less T cell infiltration when the whole tissue was analyzed. However, when the spatial localization of CD8⁺ T cells within the tissue was taken into account, levels of CXCR3 ligands and the CCR5 ligand CCL8 showed a positive association with a high relative T cell infiltration in tumor-rich areas. Thus, CXCR3 ligands could mediate T cell trafficking but CAFs could prevent T cells from reaching the malignant cells. Full article

(This article belongs to the Special Issue Tumor Microenvironment and Pancreatic Cancer)

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Review

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19 pages, 1095 KiB

Open AccessReview

The Role of the Microbiome in Pancreatic Cancer

by Koji Miyabayashi, Hideaki Ijichi and Mitsuhiro Fujishiro

Cancers 2022, 14(18), 4479; https://doi.org/10.3390/cancers14184479 - 15 Sep 2022

Cited by 11 | Viewed by 3499

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with little improvement in outcomes in recent decades, although the molecular and phenotypic characterization of PDAC has contributed to advances in tailored therapies. PDAC is characterized by dense stroma surrounding tumor cells, [...] Read more.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with little improvement in outcomes in recent decades, although the molecular and phenotypic characterization of PDAC has contributed to advances in tailored therapies. PDAC is characterized by dense stroma surrounding tumor cells, which limits the efficacy of treatment due to the creation of a physical barrier and immunosuppressive environment. Emerging evidence regarding the microbiome in PDAC implies its potential role in the initiation and progression of PDAC. However, the underlying mechanisms of how the microbiome affects the local tumor microenvironment (TME) as well as the systemic immune system have not been elucidated in PDAC. In addition, therapeutic strategies based on the microbiome have not been established. In this review, we summarize the current evidence regarding the role of the microbiome in the development of PDAC and discuss a possible role for the microbiome in the early detection of PDAC in relation to premalignant pancreatic diseases, such as chronic pancreatitis and intraductal papillary mucinous neoplasm (IPMN). In addition, we discuss the potential role of the microbiome in the treatment of PDAC, especially in immunotherapy, although the biomarkers used to predict the efficacy of immunotherapy in PDAC are still unknown. A comprehensive understanding of tumor-associated immune responses, including those involving the microbiome, holds promise for new treatments in PDAC. Full article

(This article belongs to the Special Issue Tumor Microenvironment and Pancreatic Cancer)

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27 pages, 1636 KiB

Open AccessReview

Targeting the Metabolic Rewiring in Pancreatic Cancer and Its Tumor Microenvironment

by Keisuke Yamamoto, Dosuke Iwadate, Hiroyuki Kato, Yousuke Nakai, Keisuke Tateishi and Mitsuhiro Fujishiro

Cancers 2022, 14(18), 4351; https://doi.org/10.3390/cancers14184351 - 07 Sep 2022

Cited by 15 | Viewed by 3402

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with only a few effective therapeutic options. A characteristic feature of PDAC is its unique tumor microenvironment (TME), termed desmoplasia, which shows extensive fibrosis and extracellular matrix deposition, generating highly hypoxic and nutrient-deprived conditions within [...] Read more.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with only a few effective therapeutic options. A characteristic feature of PDAC is its unique tumor microenvironment (TME), termed desmoplasia, which shows extensive fibrosis and extracellular matrix deposition, generating highly hypoxic and nutrient-deprived conditions within the tumor. To thrive in this harsh TME, PDAC undergoes extensive metabolic rewiring that includes the altered use of glucose and glutamine, constitutive activation of autophagy-lysosomal pathways, and nutrient acquisition from host cells in the TME. Notably, these properties support PDAC metabolism and mediate therapeutic resistance, including immune suppression. A deeper understanding of the unique metabolic properties of PDAC and its TME may aid in the development of novel therapeutic strategies against this deadly disease. Full article

(This article belongs to the Special Issue Tumor Microenvironment and Pancreatic Cancer)

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18 pages, 1227 KiB

Open AccessReview

The Role of Neural Signaling in the Pancreatic Cancer Microenvironment

by Ryota Takahashi, Hideaki Ijichi and Mitsuhiro Fujishiro

Cancers 2022, 14(17), 4269; https://doi.org/10.3390/cancers14174269 - 31 Aug 2022

Cited by 4 | Viewed by 2675

Abstract

Pancreatic cancer is one of the most lethal malignant diseases. Various cells in the tumor microenvironment interact with tumor cells and orchestrate to support tumor progression. Several kinds of nerves are found in the tumor microenvironment, and each plays an essential role in [...] Read more.

Pancreatic cancer is one of the most lethal malignant diseases. Various cells in the tumor microenvironment interact with tumor cells and orchestrate to support tumor progression. Several kinds of nerves are found in the tumor microenvironment, and each plays an essential role in tumor biology. Recent studies have shown that sympathetic, parasympathetic, and sensory neurons are found in the pancreatic cancer microenvironment. Neural signaling not only targets neural cells, but tumor cells and immune cells via neural receptors expressed on these cells, through which tumor growth, inflammation, and anti-tumor immunity are affected. Thus, these broad-range effects of neural signaling in the pancreatic cancer microenvironment may represent novel therapeutic targets. The modulation of neural signaling may be a therapeutic strategy targeting the whole tumor microenvironment. In this review, we describe the current understanding of the role of nerves in the tumor microenvironment of various cancers, with an emphasis on pancreatic cancer. We also discuss the underlying mechanisms and the possibility of therapeutic applications. Full article

(This article belongs to the Special Issue Tumor Microenvironment and Pancreatic Cancer)

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39 pages, 1073 KiB

Open AccessReview

Clinical Strategies Targeting the Tumor Microenvironment of Pancreatic Ductal Adenocarcinoma

by Nebojsa Skorupan, Mayrel Palestino Dominguez, Samuel L. Ricci and Christine Alewine

Cancers 2022, 14(17), 4209; https://doi.org/10.3390/cancers14174209 - 30 Aug 2022

Cited by 9 | Viewed by 4354

Abstract

Pancreatic cancer has a complex tumor microenvironment which engages in extensive crosstalk between cancer cells, cancer-associated fibroblasts, and immune cells. Many of these interactions contribute to tumor resistance to anti-cancer therapies. Here, new therapeutic strategies designed to modulate the cancer-associated fibroblast and immune [...] Read more.

Pancreatic cancer has a complex tumor microenvironment which engages in extensive crosstalk between cancer cells, cancer-associated fibroblasts, and immune cells. Many of these interactions contribute to tumor resistance to anti-cancer therapies. Here, new therapeutic strategies designed to modulate the cancer-associated fibroblast and immune compartments of pancreatic ductal adenocarcinomas are described and clinical trials of novel therapeutics are discussed. Continued advances in our understanding of the pancreatic cancer tumor microenvironment are generating stromal and immune-modulating therapeutics that may improve patient responses to anti-tumor treatment. Full article

(This article belongs to the Special Issue Tumor Microenvironment and Pancreatic Cancer)

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22 pages, 876 KiB

Open AccessReview

The Extracellular Matrix: A Key Accomplice of Cancer Stem Cell Migration, Metastasis Formation, and Drug Resistance in PDAC

by Dan Wang, Yuqiang Li, Heming Ge, Tarik Ghadban, Matthias Reeh and Cenap Güngör

Cancers 2022, 14(16), 3998; https://doi.org/10.3390/cancers14163998 - 18 Aug 2022

Cited by 21 | Viewed by 4203

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is rich in dense fibrotic stroma that are composed of extracellular matrix (ECM) proteins. A disruption of the balance between ECM synthesis and secretion and the altered expression of matrix remodeling enzymes lead to abnormal ECM dynamics in PDAC. [...] Read more.

Pancreatic ductal adenocarcinoma (PDAC) is rich in dense fibrotic stroma that are composed of extracellular matrix (ECM) proteins. A disruption of the balance between ECM synthesis and secretion and the altered expression of matrix remodeling enzymes lead to abnormal ECM dynamics in PDAC. This pathological ECM promotes cancer growth, survival, invasion, and alters the behavior of fibroblasts and immune cells leading to metastasis formation and chemotherapy resistance, which contribute to the high lethality of PDAC. Additionally, recent evidence highlights that ECM, as a major structural component of the tumor microenvironment, is a highly dynamic structure in which ECM proteins establish a physical and biochemical niche for cancer stem cells (CSCs). CSCs are characterized by self-renewal, tumor initiation, and resistance to chemotherapeutics. In this review, we will discuss the effects of the ECM on tumor biological behavior and its molecular impact on the fundamental signaling pathways in PDAC. We will also provide an overview of how the different ECM components are able to modulate CSCs properties and finally discuss the current and ongoing therapeutic strategies targeting the ECM. Given the many challenges facing current targeted therapies for PDAC, a better understanding of molecular events involving the interplay of ECM and CSC will be key in identifying more effective therapeutic strategies to eliminate CSCs and ultimately to improve survival in patients that are suffering from this deadly disease. Full article

(This article belongs to the Special Issue Tumor Microenvironment and Pancreatic Cancer)

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14 pages, 1022 KiB

Open AccessEditor’s ChoiceReview

Heterogeneity of Cancer-Associated Fibroblasts and the Tumor Immune Microenvironment in Pancreatic Cancer

by Tomohiko Shinkawa, Kenoki Ohuchida and Masafumi Nakamura

Cancers 2022, 14(16), 3994; https://doi.org/10.3390/cancers14163994 - 18 Aug 2022

Cited by 16 | Viewed by 4226

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, with a 5-year survival rate of 9%. Cancer-associated fibroblasts (CAFs) have historically been considered tumor-promoting. However, multiple studies reporting that suppression of CAFs in PDAC mouse models resulted in more aggressive tumors [...] Read more.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, with a 5-year survival rate of 9%. Cancer-associated fibroblasts (CAFs) have historically been considered tumor-promoting. However, multiple studies reporting that suppression of CAFs in PDAC mouse models resulted in more aggressive tumors and worse prognosis have suggested the existence of a tumor-suppressive population within CAFs, leading to further research on heterogeneity within CAFs. In recent years, the benefits of cancer immunotherapy have been reported in various carcinomas. Unfortunately, the efficacy of immunotherapies in PDAC has been limited, and the CAF-driven cancer immunosuppressive microenvironment has been suggested as the cause. Thus, clarification of heterogeneity within the tumor microenvironment, including CAFs and tumor immunity, is urgently needed to establish effective therapeutic strategies for PDAC. In this review, we report the latest findings on the heterogeneity of CAFs and the functions of each major CAF subtype, which have been revealed by single-cell RNA sequencing in recent years. We also describe reports of tumor-suppressive CAF subtypes and the existence of CAFs that maintain a differentiated PDAC phenotype and review the potential for targeted therapy. Full article

(This article belongs to the Special Issue Tumor Microenvironment and Pancreatic Cancer)

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13 pages, 8039 KiB

Open AccessReview

Good and Bad Stroma in Pancreatic Cancer: Relevance of Functional States of Cancer-Associated Fibroblasts

by Ryota Ando, Akihiro Sakai, Tadashi Iida, Kunio Kataoka, Yasuyuki Mizutani and Atsushi Enomoto

Cancers 2022, 14(14), 3315; https://doi.org/10.3390/cancers14143315 - 07 Jul 2022

Cited by 11 | Viewed by 3168

Abstract

A well-known feature of human pancreatic ductal adenocarcinoma (PDAC) is the extensive proliferation of cancer-associated fibroblasts (CAFs) and highly fibrotic stroma. Recent evidence, based mainly on single-cell analyses, has identified various subsets of CAFs in PDAC mouse models. However, we do not know [...] Read more.

A well-known feature of human pancreatic ductal adenocarcinoma (PDAC) is the extensive proliferation of cancer-associated fibroblasts (CAFs) and highly fibrotic stroma. Recent evidence, based mainly on single-cell analyses, has identified various subsets of CAFs in PDAC mouse models. However, we do not know how these CAF subsets are involved in the progression and drug resistance of human PDAC. Additionally, it remains unclear whether these diverse CAFs have distinct origins and are indicators of genuinely distinct CAF lineages or reflect different states of the same CAFs depending on the tumor microenvironment. Interestingly, recent preclinical studies have started to characterize the nature of cancer-restraining CAFs and have identified their markers Meflin and collagen type I alpha 1. These studies have led to the development of strategies to induce changes in CAF phenotypes using chemical reagents or recombinant viruses, and some of them have been tested in clinical studies. These strategies have the unique potential to convert the so-called bad stroma to good stroma and may also have therapeutic implications for non-cancer diseases such as fibrotic diseases. Together with recently developed sophisticated strategies that specifically target distinct CAF subsets via adoptive cell transfer therapy, vaccination, and antibody–drug conjugates, any future findings arising from these clinical efforts may expand our understanding of the significance of CAF diversity in human PDAC. Full article

(This article belongs to the Special Issue Tumor Microenvironment and Pancreatic Cancer)

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19 pages, 1023 KiB

Open AccessReview

The Desmoplastic Stroma of Pancreatic Cancer: Multilayered Levels of Heterogeneity, Clinical Significance, and Therapeutic Opportunities

by Yohei Masugi

Cancers 2022, 14(13), 3293; https://doi.org/10.3390/cancers14133293 - 05 Jul 2022

Cited by 18 | Viewed by 5849

Abstract

Pancreatic cancer remains one of the most lethal malignancies and is becoming a dramatically increasing cause of cancer-related mortality worldwide. Abundant desmoplastic stroma is a histological hallmark of pancreatic ductal adenocarcinoma. Emerging evidence suggests a promising therapeutic effect of several stroma-modifying therapies that [...] Read more.

Pancreatic cancer remains one of the most lethal malignancies and is becoming a dramatically increasing cause of cancer-related mortality worldwide. Abundant desmoplastic stroma is a histological hallmark of pancreatic ductal adenocarcinoma. Emerging evidence suggests a promising therapeutic effect of several stroma-modifying therapies that target desmoplastic stromal elements in the pancreatic cancer microenvironment. The evidence also unveils multifaceted roles of cancer-associated fibroblasts (CAFs) in manipulating pancreatic cancer progression, immunity, and chemotherapeutic response. Current state-of-the-art technologies, including single-cell transcriptomics and multiplexed tissue imaging techniques, have provided a more profound knowledge of CAF heterogeneity in real-world specimens from pancreatic cancer patients, as well as in genetically engineered mouse models. In this review, we describe recent advances in the understanding of the molecular pathology bases of pancreatic cancer desmoplastic stroma at multilayered levels of heterogeneity, namely, (1) variations in cellular and non-cellular members, including CAF subtypes and extracellular matrix (ECM) proteins; (2) geographical heterogeneity in relation to cell–cell interactions and signaling pathways at niche levels and spatial heterogeneity at locoregional levels or organ levels; and (3) intertumoral stromal heterogeneity at individual levels. This review further discusses the clinicopathological significance of desmoplastic stroma and the potential opportunities for stroma-targeted therapies against this lethal malignancy. Full article

(This article belongs to the Special Issue Tumor Microenvironment and Pancreatic Cancer)

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23 pages, 894 KiB

Open AccessReview

Pancreatic Cancer and Microenvironments: Implications of Anesthesia

by Hou-Chuan Lai, Yi-Wei Kuo, Yi-Hsuan Huang, Shun-Ming Chan, Kuang-I Cheng and Zhi-Fu Wu

Cancers 2022, 14(11), 2684; https://doi.org/10.3390/cancers14112684 - 28 May 2022

Cited by 8 | Viewed by 3155

Abstract

Pancreatic malignancy is a lethal neoplasm, as well as one of the leading causes of cancer-associated mortality, having a 5-year overall survival rate of less than 10%. The average life expectancy of patients with advanced pancreatic cancer does not exceed six months. Although [...] Read more.

Pancreatic malignancy is a lethal neoplasm, as well as one of the leading causes of cancer-associated mortality, having a 5-year overall survival rate of less than 10%. The average life expectancy of patients with advanced pancreatic cancer does not exceed six months. Although surgical excision is a favorable modality for long-term survival of pancreatic neoplasm, metastasis is initially identified in nearly 80% of the patients by the time of diagnosis, making the development of therapeutic policy for pancreatic cancer extremely daunting. Emerging evidence shows that pancreatic neoplastic cells interact intimately with a complicated microenvironment that can foster drug resistance, metastasis, or relapse in pancreatic cancer. As a result, the necessity of gaining further insight should be focused on the pancreatic microenvironment contributing to cancer progression. Numerous evidence reveals that perioperative factors, including surgical manipulation and anesthetics (e.g., propofol, volatile anesthetics, local anesthetics, epidural anesthesia/analgesia, midazolam), analgesics (e.g., opioids, non-steroidal anti-inflammatory drugs, tramadol), and anesthetic adjuvants (such as ketamine and dexmedetomidine), might alter the tumor microenvironment and cancer progression by affecting perioperative inflammatory or immune responses during cancer surgery. Therefore, the anesthesiologist plays an important role in perioperative management and may affect surgical outcomes. However, the literature on the impact of anesthesia on the pancreatic cancer microenvironment and progression is limited. This review summarizes the current knowledge of the implications of anesthesia in the pancreatic microenvironment and provides future anesthetic strategies for improving pancreatic cancer survival rates. Full article

(This article belongs to the Special Issue Tumor Microenvironment and Pancreatic Cancer)

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15 pages, 1057 KiB

Open AccessPerspective

Multiphasic Heterogeneity of Fibroblasts in the Microenvironment of Pancreatic Ductal Adenocarcinoma: Dissection and the Sum of the Dynamics

by Hideaki Ijichi

Cancers 2022, 14(19), 4880; https://doi.org/10.3390/cancers14194880 - 05 Oct 2022

Cited by 3 | Viewed by 1729

Abstract

Pancreatic cancer is still the most intractable cancer, with a 5-year survival of around 10%. To conquer the most common type, pancreatic ductal adenocarcinoma (PDAC), we need to understand its pathobiology, especially the tumor microenvironment (TME) that characteristically contains abundant stromal components, with [...] Read more.

Pancreatic cancer is still the most intractable cancer, with a 5-year survival of around 10%. To conquer the most common type, pancreatic ductal adenocarcinoma (PDAC), we need to understand its pathobiology, especially the tumor microenvironment (TME) that characteristically contains abundant stromal components, with marked fibrosis. In this Special Issue, “Tumor Microenvironment and Pancreatic Cancer”, various aspects of TME were discussed, most frequently including articles related to cancer-associated fibroblasts (CAFs) and the extracellular matrix (ECM). CAFs and ECM have been considered in favor of PDAC cells; however, surprisingly, depleting CAFs or reducing the stromal components in PDAC-model mice induced aggressive PDAC and worsened the prognosis. Subsequently, accumulating studies have elucidated evidence of the heterogeneity of CAFs and the plasticity between the subtypes. Possible cancer-promoting and -restraining properties of the CAF subtypes have been suggested, but these are yet to be fully elucidated. Here, in addition to the extensive reviews on the heterogeneity of CAFs in this Special Issue, I refer to another insight from a recent integrative study of PDAC TME, that PDAC TME can be divided into three distinct sub-tumor microenvironments (subTMEs), and the co-existence of the distinct subTMEs is associated with poor prognosis. In the subTME, the heterogeneity of each component, including CAFs, can be changed transiently through various interactions in the TME, and the sum of the transient change and dynamic plasticity might be timely tuned in the co-existence of distinct subTMEs to contribute to the poor prognosis. Thus, understanding the more detailed underlying mechanisms in this heterogeneity of TME, as well as how to control the sum of multiphasic heterogeneity, might lead to the establishment of a more desirable therapeutic strategy to conquer intractable PDAC. Full article

(This article belongs to the Special Issue Tumor Microenvironment and Pancreatic Cancer)

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8 pages, 994 KiB

Open AccessCommentary

The Tumor Immune Microenvironment in Pancreatic Ductal Adenocarcinoma: Neither Hot nor Cold

by Samuel J. S. Rubin, Raoul S. Sojwal, John Gubatan and Stephan Rogalla

Cancers 2022, 14(17), 4236; https://doi.org/10.3390/cancers14174236 - 31 Aug 2022

Cited by 13 | Viewed by 3604

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic tumor and is associated with poor prognosis and treatment response. The tumor microenvironment (TME) is recognized as an important factor in metastatic progression across cancers. Despite extensive study of the TME in PDAC, the [...] Read more.

Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic tumor and is associated with poor prognosis and treatment response. The tumor microenvironment (TME) is recognized as an important factor in metastatic progression across cancers. Despite extensive study of the TME in PDAC, the cellular and molecular signaling networks remain poorly understood, largely due to the tremendous heterogeneity across tumors. While earlier work characterized PDAC as an immunologically privileged tumor poorly recognized by the immune system, recent studies revealed the important and nuanced roles of immune cells in the pathogenesis of PDAC. Distinct lymphoid, myeloid, and stromal cell types in the TME exert opposing influences on PDAC tumor trajectory, suggesting a more complex organization than the classical “hot” versus “cold” tumor distinction. We review the pro- and antitumor immune processes found in PDAC and briefly discuss their leverage for the development of novel therapeutic approaches in the field. Full article

(This article belongs to the Special Issue Tumor Microenvironment and Pancreatic Cancer)

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