J Pathol Transl Med.  2024 Mar;58(2):49-58. 10.4132/jptm.2024.01.31.

Exploring histological predictive biomarkers for immune checkpoint inhibitor therapy response in non–small cell lung cancer

• Cho U
• Im S
• Park HS

• KMID: 2553472
• DOI: http://doi.org/10.4132/jptm.2024.01.31

Abstract

Treatment challenges persist in advanced lung cancer despite the development of therapies beyond the traditional platinum-based chemotherapy. The early 2000s marked a shift to tyrosine kinase inhibitors targeting epidermal growth factor receptor, ushering in personalized genetic-based treatment. A further significant advance was the development of immune checkpoint inhibitors (ICIs), especially for non–small cell lung cancer. These target programmed death-ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4, which enhanced the immune response against tumor cells. However, not all patients respond, and immune-related toxicities arise. This review emphasizes identifying biomarkers for ICI response prediction. While PD-L1 is a widely used, validated biomarker, its predictive accuracy is imperfect. Investigating tumor-infiltrating lymphocytes, tertiary lymphoid structure, and emerging biomarkers such as high endothelial venule, Human leukocyte antigen class I, T-cell immunoreceptors with Ig and ITIM domains, and lymphocyte activation gene-3 counts is promising. Understanding and exploring additional predictive biomarkers for ICI response are crucial for enhancing patient stratification and overall care in lung cancer treatment.

Keyword

Non-small cell lung carcinoma; Immune-checkpoint inhibitor; Biomarkers

Figure

• 

  Fig. 1. Predictive biomarkers for immune checkpoint inhibitor therapy in non–small cell lung cancer that could be observed through histological or immunohistochemical observations. CTLA-4, cytotoxic T lymphocyte antigen 4; HLA, human leukocyte antigen; LAG-3, lymphocyte activation gene-3; NK, natural killer; PD-1, programmed death-1; PD-L1, programmed death-ligand 1; TCR, T-cell receptor; TIGIT, T-cell immunoreceptors with Ig and ITIM domains; TIM-3, T cell immunoglobulin and mucin domain-3; Treg, regulatory T cells; VISTA, V-domain immunoglobulin suppressor of T cell activation.

• 

  Fig. 2. (A) Lung adenocarcinoma tumor cells are expressing programmed death-ligand 1 (PD-L1). PD-L1 is the most validated predictive biomarker of immune checkpoint inhibitors for patients with lung non-small cell carcinoma (PD-L1 clone SP263). (B) Lymphoid aggregate within lung adenocarcinoma forms a tertiary lymphoid structure. (C) The high endothelial venules are identified through positive staining with MECA-79 antibody (MECA-79 staining).

Reference

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