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Review
. 2023 Feb 16;30(2):2366-2387.
doi: 10.3390/curroncol30020181.

Immunotherapy for Metastatic Non-Small Cell Lung Cancer: Therapeutic Advances and Biomarkers

Marco Russano  1 , Giulia La Cava  1 , Alessio Cortellini  1 , Fabrizio Citarella  1 , Alessandro Galletti  2 , Giuseppina Rita Di Fazio  1 , Valentina Santo  1 , Leonardo Brunetti  1 , Alessia Vendittelli  1 , Iacopo Fioroni  1 , Francesco Pantano  1 , Giuseppe Tonini  1 , Bruno Vincenzi  1
Affiliations
Review

Immunotherapy for Metastatic Non-Small Cell Lung Cancer: Therapeutic Advances and Biomarkers

Marco Russano et al. Curr Oncol. .

Abstract

Immunotherapy has revolutionized the treatment paradigm of non-small cell lung cancer and improved patients' prognosis. Immune checkpoint inhibitors have quickly become standard frontline treatment for metastatic non-oncogene addicted disease, either as a single agent or in combination strategies. However, only a few patients have long-term benefits, and most of them do not respond or develop progressive disease during treatment. Thus, the identification of reliable predictive and prognostic biomarkers remains crucial for patient selection and guiding therapeutic choices. In this review, we provide an overview of the current strategies, highlighting the main clinical challenges and novel potential biomarkers.

Keywords: PD-1/PD-L1 antibodies; biomarkers; combination strategies; immune checkpoint inhibitors; immunotherapy; liquid biopsy; non-small cell lung cancer; tissue biomarkers.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Tissue- and blood-derived biomarkers for ICIs in NSCLC. The figure shows biomarkers detectable using tissue and blood biopsies. On the left side, the biomarkers are listed in descending order, first the tissue and then the blood ones, according to the amount of evidence and robustness of the literature data. PD-L1 expression on tumor cells remains the main biomarker, currently the only one validated in clinical practice. Genomic biomarkers including MSI and other aberrations lie in the middle position because they are findable by both tissue and liquid biopsy. On the right side, the tumor microenvironment is represented. The cancer mass differs in a cold tumor and hot tumor, the latter characterized by a higher density of tumor-infiltrating lymphocytes (TILs) and other immune cells, such as tumor-associated macrophages (TAMs). Many cell populations from TME, including immune cells and circulating tumor cells (CTCs), flow into the bloodstream and can be analyzed through liquid biopsy. Promising data on biomarkers research comes from cell-free nucleic acids (cfNA), especially microRNAs (miRNA) derived from extracellular vesicles (EVs), especially exosomes.
See this image and copyright information in PMC

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