高原发率的一级抗性和不可避免的二级抗性是免疫治疗非小细胞肺癌（NSCLC）患者长期受益的主要临床障碍。NSCLC免疫治疗抗性的机制复杂，主要涉及肿瘤细胞和肿瘤微环境（TME）浸润的免疫细胞，包括TAM、B细胞、NK细胞和T细胞。在免疫治疗抗性后的NSCLC进展的临床策略选择应取决于其进展模式。NSCLC患者在免疫治疗抗性后的进展模式可划分为寡发性进展和全身/多发性进展，应进一步考虑进一步的治疗选择。未来，需要探索如何优化联合治疗并探索在抗肿瘤治疗期间如何重新编程浸润的免疫细胞，并及时重塑TME，以适应肿瘤细胞各种基因背景。Copyright © 2023 Zhou and Yang.

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.Copyright © 2023 Zhou and Yang.