38
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Cancer-associated fibroblasts (CAFs), a stromal cell population with cell-of-origin, phenotypic and functional heterogeneity, are the most essential components of the tumor microenvironment (TME). Through multiple pathways, activated CAFs can promote tumor growth, angiogenesis, invasion and metastasis, along with extracellular matrix (ECM) remodeling and even chemoresistance. Numerous previous studies have confirmed the critical role of the interaction between CAFs and tumor cells in tumorigenesis and development. However, recently, the mutual effects of CAFs and the tumor immune microenvironment (TIME) have been identified as another key factor in promoting tumor progression. The TIME mainly consists of distinct immune cell populations in tumor islets and is highly associated with the antitumor immunological state in the TME. CAFs interact with tumor-infiltrating immune cells as well as other immune components within the TIME via the secretion of various cytokines, growth factors, chemokines, exosomes and other effector molecules, consequently shaping an immunosuppressive TME that enables cancer cells to evade surveillance of the immune system. In-depth studies of CAFs and immune microenvironment interactions, particularly the complicated mechanisms connecting CAFs with immune cells, might provide novel strategies for subsequent targeted immunotherapies. Herein, we shed light on recent advances regarding the direct and indirect crosstalk between CAFs and infiltrating immune cells and further summarize the possible immunoinhibitory mechanisms induced by CAFs in the TME. In addition, we present current related CAF-targeting immunotherapies and briefly describe some future perspectives on CAF research in the end.

          Related collections

          Most cited references350

          • Record: found
          • Abstract: found
          • Article: not found

          Microenvironmental regulation of tumor progression and metastasis.

          Cancers develop in complex tissue environments, which they depend on for sustained growth, invasion and metastasis. Unlike tumor cells, stromal cell types within the tumor microenvironment (TME) are genetically stable and thus represent an attractive therapeutic target with reduced risk of resistance and tumor recurrence. However, specifically disrupting the pro-tumorigenic TME is a challenging undertaking, as the TME has diverse capacities to induce both beneficial and adverse consequences for tumorigenesis. Furthermore, many studies have shown that the microenvironment is capable of normalizing tumor cells, suggesting that re-education of stromal cells, rather than targeted ablation per se, may be an effective strategy for treating cancer. Here we discuss the paradoxical roles of the TME during specific stages of cancer progression and metastasis, as well as recent therapeutic attempts to re-educate stromal cells within the TME to have anti-tumorigenic effects.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            TGF-β attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells

            Therapeutic antibodies that block the programmed death-ligand 1 (PD-L1)/programmed death-1 (PD-1) pathway can induce robust and durable responses in patients with various cancers, including metastatic urothelial cancer (mUC) 1–5 . However, these responses only occur in a subset of patients. Elucidating the determinants of response and resistance is key to improving outcomes and developing new treatment strategies. Here, we examined tumours from a large cohort of mUC patients treated with an anti–PD-L1 agent (atezolizumab) and identified major determinants of clinical outcome. Response was associated with CD8+ T-effector cell phenotype and, to an even greater extent, high neoantigen or tumour mutation burden (TMB). Lack of response was associated with a signature of transforming growth factor β (TGF-β) signalling in fibroblasts, particularly in patients with CD8+ T cells that were excluded from the tumour parenchyma and instead found in the fibroblast- and collagen-rich peritumoural stroma—a common phenotype among patients with mUC. Using a mouse model that recapitulates this immune excluded phenotype, we found that therapeutic administration of a TGF-β blocking antibody together with anti–PD-L1 reduced TGF-β signalling in stromal cells, facilitated T cell penetration into the centre of the tumour, and provoked vigorous anti-tumour immunity and tumour regression. Integration of these three independent biological features provides the best basis for understanding outcome in this setting and suggests that TGF-β shapes the tumour microenvironment to restrain anti-tumour immunity by restricting T cell infiltration.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Cancer-related inflammation.

              The mediators and cellular effectors of inflammation are important constituents of the local environment of tumours. In some types of cancer, inflammatory conditions are present before a malignant change occurs. Conversely, in other types of cancer, an oncogenic change induces an inflammatory microenvironment that promotes the development of tumours. Regardless of its origin, 'smouldering' inflammation in the tumour microenvironment has many tumour-promoting effects. It aids in the proliferation and survival of malignant cells, promotes angiogenesis and metastasis, subverts adaptive immune responses, and alters responses to hormones and chemotherapeutic agents. The molecular pathways of this cancer-related inflammation are now being unravelled, resulting in the identification of new target molecules that could lead to improved diagnosis and treatment.
                Bookmark

                Author and article information

                Contributors
                mengqingcai@fudanpci.org
                yuxianjun@fudanpci.org
                shisi@fudanpci.org
                Journal
                Mol Cancer
                Mol Cancer
                Molecular Cancer
                BioMed Central (London )
                1476-4598
                11 October 2021
                11 October 2021
                2021
                : 20
                : 131
                Affiliations
                [1 ]GRID grid.452404.3, ISNI 0000 0004 1808 0942, Department of Pancreatic Surgery, , Fudan University Shanghai Cancer Center, ; No. 270 Dong’An Road, Xuhui District, Shanghai, 200032 China
                [2 ]GRID grid.8547.e, ISNI 0000 0001 0125 2443, Department of Oncology, Shanghai Medical College, , Fudan University, ; Shanghai, 200032 China
                [3 ]GRID grid.452404.3, ISNI 0000 0004 1808 0942, Shanghai Pancreatic Cancer Institute, ; Shanghai, 200032 China
                [4 ]GRID grid.8547.e, ISNI 0000 0001 0125 2443, Pancreatic Cancer Institute, , Fudan University, ; Shanghai, 200032 China
                Author information
                http://orcid.org/0000-0002-6652-0629
                Article
                1428
                10.1186/s12943-021-01428-1
                8504100
                34635121
                12adea6b-e967-4c89-acbf-f032143d2848
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 1 July 2021
                : 11 September 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, national natural science foundation of china;
                Award ID: 81802352
                Award ID: 81772555
                Award ID: 81902428
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100005153, china national funds for distinguished young scientists;
                Award ID: 81625016
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100013105, shanghai rising-star program;
                Award ID: 20QA1402100
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2021

                Oncology & Radiotherapy
                cancer-associated fibroblasts,tumor-infiltrating immune cells,tumor microenvironment,tumor immune microenvironment,cell–cell interaction,immune suppression,caf-targeted therapy,cancer

                Comments

                Comment on this article