Current literature review on the tumor immune micro-environment, its heterogeneity and future perspectives in treatment of advanced non-small cell lung cancer

Jeong Uk Lim; Eunyoung Lee; Sang-Yun Lee; Hyeong Jun Cho; Dong Hyuck Ahn; Yongki Hwang; Joon Young Choi; Chang Dong Yeo; Chan Kwon Park; Seung Joon Kim

doi:10.21037/tlcr-22-633

Current literature review on the tumor immune micro-environment, its heterogeneity and future perspectives in treatment of advanced non-small cell lung cancer

Transl Lung Cancer Res. 2023 Apr 28;12(4):857-876. doi: 10.21037/tlcr-22-633. Epub 2023 Mar 17.

Authors

Jeong Uk Lim¹, Eunyoung Lee^{2

3}, Sang-Yun Lee⁴, Hyeong Jun Cho^{2

3}, Dong Hyuck Ahn^{2

3}, Yongki Hwang³, Joon Young Choi⁵, Chang Dong Yeo⁶, Chan Kwon Park¹, Seung Joon Kim^{2

3}

Affiliations

¹ Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
² Division of Pulmonology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
³ Postech-Catholic Biomedical Engineering Institute, Songeui Multiplex Hall, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
⁴ Department of Biomedical Engineering, Gachon University, Seongnam, Republic of Korea.
⁵ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
⁶ Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Abstract

Background and objective: Immune checkpoint inhibitors (ICI) were a major clinical advancement that provided an opportunity to improve the prognosis of patients with non-small cell lung cancer (NSCLC). However, programmed death-ligand-1 (PD-L1) expression does not sufficiently predict ICI efficacy in NSCLC patients. In recent studies, the tumor immune microenvironment (TIME) was shown to have a central role in lung cancer progression and to affect clinical outcome of patients diagnosed with lung cancer. As development of new therapeutic targets to overcome ICI resistance is a priority, understanding the TIME is important. Recently, a series of studies was conducted to target each component of TIME to improve efficacy of cancer treatment. In this review, important features related to TIME, its heterogeneity and current trends in treatment targeting the component of TIME are discussed.

Methods: PubMed and PMC were searched from January 1st, 2012 to August 16th, 2022 using the following key words: "NSCLC", "Tumor microenvironment", "Immune", "Metastasis" and "Heterogeneity".

Key content and findings: Heterogeneity in the TIME can be either spatial or temporal. Subsequent to heterogeneous changes in the TIME, treatment of lung cancer can be more challenging because drug resistance is more likely to occur. In terms of the TIME, the main concept for increasing the chance of successful NSCLC treatment is to activate immune responses against tumor cells and inhibit immunosuppressive activities. In addition, relevant research is focused on normalizing an otherwise aberrant TIME in NSCLC patients. Potential therapeutic targets include immune cells, cytokine interactions, and non-immune cells such as fibroblasts or vessels.

Conclusions: In management of lung cancer, understanding TIME and its heterogeneity is significant to treatment outcomes. Ongoing trials including various treatment modalities such as radiotherapy, cytotoxic chemotherapy, and anti-angiogenic treatment and regimens inhibiting other immunoinhibitory molecules are promising.

Keywords: Tumor microenvironment; heterogeneity; immune; immunotherapy; non-small cell lung cancer (NSCLC).

Publication types

Review