Immunotherapy resistance in non-small-cell lung cancer: From mechanism to clinical strategies

Front Immunol. 2023 Apr 6:14:1129465. doi: 10.3389/fimmu.2023.1129465. eCollection 2023.

Abstract

The high primary resistance incidence and unavoidable secondary resistance are the major clinical obstacle to lasting long-term benefits in Non-small-cell lung cancer (NSCLC) patients treated with immunotherapy. The mechanisms of immunotherapy resistance in NSCLC are complex, mainly involving tumor cells and tumor microenvironment (TME) infiltrating immune cells, including TAMs, B cells, NK cells, and T cells. The selection of clinical strategies for NSCLC progression after immunotherapy resistance should depend on the progressive mode. The progression pattern of NSCLC patients after immunotherapy resistance can be divided into oligo-progression and systemic/multiple progression, which should be considered for further treatment selection. In the future, it needs to explore how to optimize the combined therapy and explore strategies to reprogram infiltrating immune cells under various genetic backgrounds of tumor cells and timely reshape TME during antitumor treatments.

Keywords: NSCLC; TME; clinical strategies; immune cells; immunotherapy.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Humans
  • Immunotherapy
  • Lung Neoplasms* / drug therapy
  • T-Lymphocytes / pathology
  • Tumor Microenvironment

Grants and funding

This study was supported by National Natural Science Foundation of China (NSFC 81872458), and Xi’an Health Commission (2022ms11).