Non-small cell lung cancer and the tumor microenvironment: making headway from targeted therapies to advanced immunotherapy
Over the past decades, significant progress has been made in the understanding of non-small cell lung cancer (NSCLC) biology and tumor progression mechanisms, resulting in the development of novel strategies for early detection and wide-ranging care approaches. Since their introduction, over 20 year...
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| Language: | English |
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1515748/full |
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| author | Anna De Lucia Lucia Mazzotti Lucia Mazzotti Anna Gaimari Anna Gaimari Matteo Zurlo Roberta Maltoni Claudio Cerchione Sara Bravaccini Angelo Delmonte Lucio Crinò Patricia Borges de Souza Luigi Pasini Fabio Nicolini Fabrizio Bianchi Manel Juan Hugo Calderon Chiara Magnoni Chiara Magnoni Luca Gazzola Luca Gazzola Paola Ulivi Massimiliano Mazza |
| author_facet | Anna De Lucia Lucia Mazzotti Lucia Mazzotti Anna Gaimari Anna Gaimari Matteo Zurlo Roberta Maltoni Claudio Cerchione Sara Bravaccini Angelo Delmonte Lucio Crinò Patricia Borges de Souza Luigi Pasini Fabio Nicolini Fabrizio Bianchi Manel Juan Hugo Calderon Chiara Magnoni Chiara Magnoni Luca Gazzola Luca Gazzola Paola Ulivi Massimiliano Mazza |
| author_sort | Anna De Lucia |
| collection | DOAJ |
| description | Over the past decades, significant progress has been made in the understanding of non-small cell lung cancer (NSCLC) biology and tumor progression mechanisms, resulting in the development of novel strategies for early detection and wide-ranging care approaches. Since their introduction, over 20 years ago, targeted therapies with tyrosine kinase inhibitors (TKIs) have revolutionized the treatment landscape for NSCLC. Nowadays, targeted therapies remain the gold standard for many patients, but still they suffer from many adverse effects, including unexpected toxicity and intrinsic acquired resistance mutations, which lead to relapse. The adoption of immune checkpoint inhibitors (ICIs) in 2015, has offered exceptional survival benefits for patients without targetable alterations. Despite this notable progress, challenges remain, as not all patients respond favorably to ICIs, and resistance to therapy can develop over time. A crucial factor influencing clinical response to immunotherapy is the tumor microenvironment (TME). The TME is pivotal in orchestrating the interactions between neoplastic cells and the immune system, influencing tumor growth and treatment outcomes. In this review, we discuss how the understanding of this intricate relationship is crucial for the success of immunotherapy and survey the current state of immunotherapy intervention, with a focus on forthcoming and promising chimeric antigen receptor (CAR) T cell therapies in NSCLC. The TME sets major obstacles for CAR-T therapies, creating conditions that suppress the immune response, inducing T cell exhaustion. To enhance treatment efficacy, specific efforts associated with CAR-T cell therapy in NSCLC, should definitely focus TME-related immunosuppression and antigen escape mechanisms, by combining CAR-T cells with immune checkpoint blockades. |
| format | Article |
| id | doaj-art-347344ab850540eabafa2866681babe2 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-347344ab850540eabafa2866681babe22025-02-10T05:16:08ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15157481515748Non-small cell lung cancer and the tumor microenvironment: making headway from targeted therapies to advanced immunotherapyAnna De Lucia0Lucia Mazzotti1Lucia Mazzotti2Anna Gaimari3Anna Gaimari4Matteo Zurlo5Roberta Maltoni6Claudio Cerchione7Sara Bravaccini8Angelo Delmonte9Lucio Crinò10Patricia Borges de Souza11Luigi Pasini12Fabio Nicolini13Fabrizio Bianchi14Manel Juan15Hugo Calderon16Chiara Magnoni17Chiara Magnoni18Luca Gazzola19Luca Gazzola20Paola Ulivi21Massimiliano Mazza22Advanced Cellular Therapies and Rare Tumors Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyAdvanced Cellular Therapies and Rare Tumors Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyDepartment of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, ItalyAdvanced Cellular Therapies and Rare Tumors Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyDepartment of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, ItalyAdvanced Cellular Therapies and Rare Tumors Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyHealthcare Administration, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyHematology Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyDepartment of Medicine and Surgery, “Kore” University of Enna, Enna, ItalyMedical Oncology Department, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyMedical Oncology Department, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyAdvanced Cellular Therapies and Rare Tumors Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyAdvanced Cellular Therapies and Rare Tumors Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyAdvanced Cellular Therapies and Rare Tumors Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyUnit of Cancer Biomarker, Fondazione IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo, FG, ItalyDepartment of Immunology, Institut D’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, SpainDepartment of Immunology, Institut D’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, SpainAdvanced Cellular Therapies and Rare Tumors Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyDepartment of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, ItalyAdvanced Cellular Therapies and Rare Tumors Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyDepartment of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, ItalyTranslational Oncology Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyAdvanced Cellular Therapies and Rare Tumors Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyOver the past decades, significant progress has been made in the understanding of non-small cell lung cancer (NSCLC) biology and tumor progression mechanisms, resulting in the development of novel strategies for early detection and wide-ranging care approaches. Since their introduction, over 20 years ago, targeted therapies with tyrosine kinase inhibitors (TKIs) have revolutionized the treatment landscape for NSCLC. Nowadays, targeted therapies remain the gold standard for many patients, but still they suffer from many adverse effects, including unexpected toxicity and intrinsic acquired resistance mutations, which lead to relapse. The adoption of immune checkpoint inhibitors (ICIs) in 2015, has offered exceptional survival benefits for patients without targetable alterations. Despite this notable progress, challenges remain, as not all patients respond favorably to ICIs, and resistance to therapy can develop over time. A crucial factor influencing clinical response to immunotherapy is the tumor microenvironment (TME). The TME is pivotal in orchestrating the interactions between neoplastic cells and the immune system, influencing tumor growth and treatment outcomes. In this review, we discuss how the understanding of this intricate relationship is crucial for the success of immunotherapy and survey the current state of immunotherapy intervention, with a focus on forthcoming and promising chimeric antigen receptor (CAR) T cell therapies in NSCLC. The TME sets major obstacles for CAR-T therapies, creating conditions that suppress the immune response, inducing T cell exhaustion. To enhance treatment efficacy, specific efforts associated with CAR-T cell therapy in NSCLC, should definitely focus TME-related immunosuppression and antigen escape mechanisms, by combining CAR-T cells with immune checkpoint blockades.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1515748/fullnon-small cell lung cancer (NSCLC)tumor microenvironment (TME)tyrosine kinase inhibitors (TKIs)immune checkpoint inhibitors (ICIs)chimeric antigen receptor (CAR) T cell therapy |
| spellingShingle | Anna De Lucia Lucia Mazzotti Lucia Mazzotti Anna Gaimari Anna Gaimari Matteo Zurlo Roberta Maltoni Claudio Cerchione Sara Bravaccini Angelo Delmonte Lucio Crinò Patricia Borges de Souza Luigi Pasini Fabio Nicolini Fabrizio Bianchi Manel Juan Hugo Calderon Chiara Magnoni Chiara Magnoni Luca Gazzola Luca Gazzola Paola Ulivi Massimiliano Mazza Non-small cell lung cancer and the tumor microenvironment: making headway from targeted therapies to advanced immunotherapy Frontiers in Immunology non-small cell lung cancer (NSCLC) tumor microenvironment (TME) tyrosine kinase inhibitors (TKIs) immune checkpoint inhibitors (ICIs) chimeric antigen receptor (CAR) T cell therapy |
| title | Non-small cell lung cancer and the tumor microenvironment: making headway from targeted therapies to advanced immunotherapy |
| title_full | Non-small cell lung cancer and the tumor microenvironment: making headway from targeted therapies to advanced immunotherapy |
| title_fullStr | Non-small cell lung cancer and the tumor microenvironment: making headway from targeted therapies to advanced immunotherapy |
| title_full_unstemmed | Non-small cell lung cancer and the tumor microenvironment: making headway from targeted therapies to advanced immunotherapy |
| title_short | Non-small cell lung cancer and the tumor microenvironment: making headway from targeted therapies to advanced immunotherapy |
| title_sort | non small cell lung cancer and the tumor microenvironment making headway from targeted therapies to advanced immunotherapy |
| topic | non-small cell lung cancer (NSCLC) tumor microenvironment (TME) tyrosine kinase inhibitors (TKIs) immune checkpoint inhibitors (ICIs) chimeric antigen receptor (CAR) T cell therapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1515748/full |
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