Therapeutic Implications of Tumor Microenvironment in Lung Cancer: Focus on Immune Checkpoint Blockade
In the last decade, the treatment of non-small cell lung cancer (NSCLC) has been revolutionized by the introduction of immune checkpoint inhibitors (ICI) directed against programmed death protein 1 (PD-1) and its ligand (PD-L1), or cytotoxic T lymphocyte antigen 4 (CTLA-4). In spite of these improve...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.799455/full |
| _version_ | 1818750145679851520 |
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| author | Carlo Genova Carlo Genova Chiara Dellepiane Paolo Carrega Sara Sommariva Sara Sommariva Guido Ferlazzo Paolo Pronzato Rosaria Gangemi Gilberto Filaci Gilberto Filaci Simona Coco Michela Croce |
| author_facet | Carlo Genova Carlo Genova Chiara Dellepiane Paolo Carrega Sara Sommariva Sara Sommariva Guido Ferlazzo Paolo Pronzato Rosaria Gangemi Gilberto Filaci Gilberto Filaci Simona Coco Michela Croce |
| author_sort | Carlo Genova |
| collection | DOAJ |
| description | In the last decade, the treatment of non-small cell lung cancer (NSCLC) has been revolutionized by the introduction of immune checkpoint inhibitors (ICI) directed against programmed death protein 1 (PD-1) and its ligand (PD-L1), or cytotoxic T lymphocyte antigen 4 (CTLA-4). In spite of these improvements, some patients do not achieve any benefit from ICI, and inevitably develop resistance to therapy over time. Tumor microenvironment (TME) might influence response to immunotherapy due to its prominent role in the multiple interactions between neoplastic cells and the immune system. Studies investigating lung cancer from the perspective of TME pointed out a complex scenario where tumor angiogenesis, soluble factors, immune suppressive/regulatory elements and cells composing TME itself participate to tumor growth. In this review, we point out the current state of knowledge involving the relationship between tumor cells and the components of TME in NSCLC as well as their interactions with immunotherapy providing an update on novel predictors of benefit from currently employed ICI or new therapeutic targets of investigational agents. In first place, increasing evidence suggests that TME might represent a promising biomarker of sensitivity to ICI, based on the presence of immune-modulating cells, such as Treg, myeloid derived suppressor cells, and tumor associated macrophages, which are known to induce an immunosuppressive environment, poorly responsive to ICI. Consequently, multiple clinical studies have been designed to influence TME towards a pro-immunogenic state and subsequently improve the activity of ICI. Currently, the mostly employed approach relies on the association of “classic” ICI targeting PD-1/PD-L1 and novel agents directed on molecules, such as LAG-3 and TIM-3. To date, some trials have already shown promising results, while a multitude of prospective studies are ongoing, and their results might significantly influence the future approach to cancer immunotherapy. |
| first_indexed | 2024-12-18T04:15:01Z |
| format | Article |
| id | doaj.art-fdf9dff0eeab48d6bc67db88fdefbeb5 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-18T04:15:01Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-fdf9dff0eeab48d6bc67db88fdefbeb52022-12-21T21:21:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-01-011210.3389/fimmu.2021.799455799455Therapeutic Implications of Tumor Microenvironment in Lung Cancer: Focus on Immune Checkpoint BlockadeCarlo Genova0Carlo Genova1Chiara Dellepiane2Paolo Carrega3Sara Sommariva4Sara Sommariva5Guido Ferlazzo6Paolo Pronzato7Rosaria Gangemi8Gilberto Filaci9Gilberto Filaci10Simona Coco11Michela Croce12UO Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, ItalyDipartimento di Medicina Interna e Specialità Mediche (DIMI), Università degli Studi di Genova, Genova, ItalyLung Cancer Unit, IRCCS Ospedale Policlinico San Martino, Genova, ItalyDipartimento di Patologia Umana, University of Messina, Messina, ItalySuPerconducting and Other INnovative Materials and Devices Institute, Consiglio Nazionale delle Ricerche (CNR-SPIN), Genova, ItalyLife Science Computational Laboratory (LISCOMP), IRCCS Ospedale Policlinico San Martino, Genova, ItalyDipartimento di Patologia Umana, University of Messina, Messina, ItalyUO Oncologia Medica 2, IRCCS Ospedale Policlinico San Martino, Genova, ItalyUO Bioterapie, IRCCS Ospedale Policlinico San Martino, Genova, ItalyDipartimento di Medicina Interna e Specialità Mediche (DIMI), Università degli Studi di Genova, Genova, ItalyUO Bioterapie, IRCCS Ospedale Policlinico San Martino, Genova, ItalyLung Cancer Unit, IRCCS Ospedale Policlinico San Martino, Genova, ItalyUO Bioterapie, IRCCS Ospedale Policlinico San Martino, Genova, ItalyIn the last decade, the treatment of non-small cell lung cancer (NSCLC) has been revolutionized by the introduction of immune checkpoint inhibitors (ICI) directed against programmed death protein 1 (PD-1) and its ligand (PD-L1), or cytotoxic T lymphocyte antigen 4 (CTLA-4). In spite of these improvements, some patients do not achieve any benefit from ICI, and inevitably develop resistance to therapy over time. Tumor microenvironment (TME) might influence response to immunotherapy due to its prominent role in the multiple interactions between neoplastic cells and the immune system. Studies investigating lung cancer from the perspective of TME pointed out a complex scenario where tumor angiogenesis, soluble factors, immune suppressive/regulatory elements and cells composing TME itself participate to tumor growth. In this review, we point out the current state of knowledge involving the relationship between tumor cells and the components of TME in NSCLC as well as their interactions with immunotherapy providing an update on novel predictors of benefit from currently employed ICI or new therapeutic targets of investigational agents. In first place, increasing evidence suggests that TME might represent a promising biomarker of sensitivity to ICI, based on the presence of immune-modulating cells, such as Treg, myeloid derived suppressor cells, and tumor associated macrophages, which are known to induce an immunosuppressive environment, poorly responsive to ICI. Consequently, multiple clinical studies have been designed to influence TME towards a pro-immunogenic state and subsequently improve the activity of ICI. Currently, the mostly employed approach relies on the association of “classic” ICI targeting PD-1/PD-L1 and novel agents directed on molecules, such as LAG-3 and TIM-3. To date, some trials have already shown promising results, while a multitude of prospective studies are ongoing, and their results might significantly influence the future approach to cancer immunotherapy.https://www.frontiersin.org/articles/10.3389/fimmu.2021.799455/fullNSCLCPD-1/PD-L1CTLA-4tumor microenvironment (TME)immune checkpoint inhibitorsdysfunctional T cells |
| spellingShingle | Carlo Genova Carlo Genova Chiara Dellepiane Paolo Carrega Sara Sommariva Sara Sommariva Guido Ferlazzo Paolo Pronzato Rosaria Gangemi Gilberto Filaci Gilberto Filaci Simona Coco Michela Croce Therapeutic Implications of Tumor Microenvironment in Lung Cancer: Focus on Immune Checkpoint Blockade Frontiers in Immunology NSCLC PD-1/PD-L1 CTLA-4 tumor microenvironment (TME) immune checkpoint inhibitors dysfunctional T cells |
| title | Therapeutic Implications of Tumor Microenvironment in Lung Cancer: Focus on Immune Checkpoint Blockade |
| title_full | Therapeutic Implications of Tumor Microenvironment in Lung Cancer: Focus on Immune Checkpoint Blockade |
| title_fullStr | Therapeutic Implications of Tumor Microenvironment in Lung Cancer: Focus on Immune Checkpoint Blockade |
| title_full_unstemmed | Therapeutic Implications of Tumor Microenvironment in Lung Cancer: Focus on Immune Checkpoint Blockade |
| title_short | Therapeutic Implications of Tumor Microenvironment in Lung Cancer: Focus on Immune Checkpoint Blockade |
| title_sort | therapeutic implications of tumor microenvironment in lung cancer focus on immune checkpoint blockade |
| topic | NSCLC PD-1/PD-L1 CTLA-4 tumor microenvironment (TME) immune checkpoint inhibitors dysfunctional T cells |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.799455/full |
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