Non-small cell lung cancer and the tumor microenvironment: making headway from targeted therapies to advanced immunotherapy

被引：0

作者：

De Lucia, Anna ^{[1
]}

Mazzotti, Lucia ^{[1
,2
]}

Gaimari, Anna ^{[1
,2
]}

Zurlo, Matteo ^{[1
]}

Maltoni, Roberta ^{[3
]}

Cerchione, Claudio ^{[4
]}

Bravaccini, Sara ^{[5
]}

Delmonte, Angelo ^{[6
]}

Crino, Lucio ^{[6
]}

de Souza, Patricia Borges ^{[1
]}

Pasini, Luigi ^{[1
,10
]}

Nicolini, Fabio ^{[1
]}

Bianchi, Fabrizio ^{[7
]}

Juan, Manel ^{[8
]}

Calderon, Hugo ^{[8
]}

Magnoni, Chiara ^{[1
,2
]}

Gazzola, Luca ^{[1
,2
]}

Ulivi, Paola ^{[9
]}

Mazza, Massimiliano ^{[1
]}

机构：

[1] IRCCS Ist Romagnolo Studio Tumori IRST Dino Amador, Adv Cellular Therapies & Rare Tumors Unit, Meldola, Italy

[2] Univ Bologna, Dept Biomed & Neuromotor Sci, Bologna, Italy

[3] IRCCS Ist Romagnolo Studio Tumori IRST Dino Amador, Healthcare Adm, Meldola, Italy

[4] IRCCS Ist Romagnolo Studio Tumori IRST Dino Amador, Hematol Unit, Meldola, Italy

[5] Kore Univ Enna, Dept Med & Surg, Enna, Italy

[6] IRCCS Ist Romagnolo Studio Tumori IRST Dino Amador, Med Oncol Dept, Meldola, Italy

[7] Fdn IRCCS Casa Sollievo Sofferenza, Unit Canc Biomarker, San Giovanni Rotondo, FG, Italy

[8] Inst Invest Biomed August Pi i Sunyer IDIBAPS, Dept Immunol, Barcelona, Spain

[9] IRCCS Ist Romagnolo Studio Tumori IRST Dino Amador, Translat Oncol Unit, Meldola, Italy

[10] IRCCS Ist Romagnolo Studio Tumori IRST Dino Amador, Meldola, FC, Italy

来源：

FRONTIERS IN IMMUNOLOGY | 2025年 / 16卷

关键词：

non-small cell lung cancer (NSCLC); tumor microenvironment (TME); tyrosine kinase inhibitors (TKIs); immune checkpoint inhibitors (ICIs); chimeric antigen receptor (CAR) T cell therapy; CHIMERIC ANTIGEN RECEPTOR; CAR-T-CELLS; TERTIARY LYMPHOID STRUCTURES; GROWTH-FACTOR RECEPTOR; OPEN-LABEL; EGFR-MUTATION; 1ST-LINE TREATMENT; ACQUIRED-RESISTANCE; IMMUNE CELLS; SOLID TUMORS;

D O I：

10.3389/fimmu.2025.1515748

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页数：21

共 162 条

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