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Tumor immune microenvironment predicts the pathologic response of neoadjuvant chemoimmunotherapy in non-small-cell lung cancer.

ABSTRACT: The clinical outcome of resectable non-small-cell lung cancer (NSCLC) patients receiving neoadjuvant chemoimmunotherapy is good but varies greatly. In addition, the pathological response after neoadjuvant chemoimmunotherapy is significantly associated with survival outcomes. The aim of this retrospective study was to identify which population of patients with locally advanced and oligometastatic NSCLC has a favorable pathological response after neoadjuvant chemoimmunotherapy. NSCLC patients treated with neoadjuvant chemoimmunotherapy were enrolled between February 2018 and April 2022. Data on clinicopathological features were collected and evaluated. Multiplex immunofluorescence was performed on pre-treatment puncture specimens and surgically resected specimens. In total, 29 patients with stages III and IV locally advanced or oligometastatic NSCLC who received neoadjuvant chemoimmunotherapy and R0 resection were enrolled. The results showed that 55% (16/29) of patients had a major pathological response (MPR) and 41% (12/29) of patients had a complete pathological response (pCR). In the stroma area of the pre-treatment specimen, the higher infiltration of CD3⁺ PD-L1⁺ tumor-infiltrating lymphocytes (TILs) and the lower infiltration of CD4⁺ and CD4⁺ FOXP3⁺ TILs were more likely to appear in patients with pCR. However, in the tumor area, the higher infiltration of CD8⁺ TILs was more likely to appear in patients with non-MPR. In the post-treatment specimen, we found increased infiltration of CD3⁺ CD8⁺ , CD8⁺ GZMB⁺ , and CD8⁺ CD69⁺ TILs and decreased infiltration of PD-1⁺ TILs both in the stroma and tumor areas. Neoadjuvant chemoimmunotherapy achieved an MPR rate of 55% and induced greater immune infiltration. In addition, we observed that the baseline TILs and their spatial distribution correlate to the pathological response.

SUBMITTER: Han R

PROVIDER: S-EPMC10236616 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Tumor immune microenvironment predicts the pathologic response of neoadjuvant chemoimmunotherapy in non-small-cell lung cancer.

Han Rui R Zhang Yimin Y Wang Tianhu T Xiao Hualiang H Luo Zhilin Z Shen Cheng C Li Jianghua J Zhao Chenglong C Li Li L Zhu Mengxiao M Du Haiwei H Tang Huan H Ma Zheng Z Wang Yubo Y He Yong Y

Cancer science 20230326 6

The clinical outcome of resectable non-small-cell lung cancer (NSCLC) patients receiving neoadjuvant chemoimmunotherapy is good but varies greatly. In addition, the pathological response after neoadjuvant chemoimmunotherapy is significantly associated with survival outcomes. The aim of this retrospective study was to identify which population of patients with locally advanced and oligometastatic NSCLC has a favorable pathological response after neoadjuvant chemoimmunotherapy. NSCLC patients trea ...[more]

PMID: 36880750

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Project description:BackgroundSleeve lobectomy has been reported to be a safe procedure after neoadjuvant chemotherapy. We aim to evaluate the oncological and surgical outcomes of neoadjuvant chemoimmunotherapy (IO+C) for local advanced non-small cell lung cancer (NSCLC) patients who underwent sleeve lobectomy.MethodsNSCLC patients that underwent sleeve lobectomy between December 2016 and December 2019 were retrospectively included. Patients were divided into two groups: neoadjuvant IO+C and chemotherapy. Oncological, intraoperative and postoperative variables were compared.ResultsIn total, 20 patients underwent sleeve lobectomy after neoadjuvant IO+C (n=10) or chemotherapy (n=10). In the neoadjuvant IO+C group, 8/10 (80%) patients achieved a partial response (PR), 1/10 (10%) patients had a complete pathological response (CPR), and 5/10 (50%) patients achieved a major pathological response (MPR). In the neoadjuvant chemotherapy group, only 3/10 (30%) patients had PR, and 3/10 (30%) patients achieved MPR. No complications were found in the neoadjuvant IO+C group, 1 chylothorax occurred in the neoadjuvant chemotherapy group. Other peri- and postoperative outcomes were similar: bleeding volume (365.00 vs. 347.50 mL; P=0.267), operation time (291.88 vs. 287.50 min; P=0.886), chest tube duration (5.40 vs. 5.00 day; P=0.829), total drainage volume (815.50 vs. 842.50 mL; P=0.931) and the length of hospital-stay (7.00 vs. 6.56 day; P=0.915). In addition, less N1 (average number 4.70 vs. 7.40) and N2 (average number 9.80 vs. 20.10) lymph nodes were acquired in the neoadjuvant IO+C group than the neoadjuvant chemotherapy group. The number of lymph nodes positive for tumor cells was also less in the neoadjuvant IO+C group than the neoadjuvant chemotherapy group, both in N1 (0.40 vs. 1.60) and N2 (0.10 vs. 1.30). The positive lymph node ratio (LNR) was lower in the neoadjuvant IO+C group, both in N1 (0.05 vs. 0.15) and N2 (0.01 vs. 0.09). A greater destruction on elastic fiber of the blood vessels, vascular wall degeneration, fibrinoid necrosis and fibrosis, and greater pulmonary interstitial exudation were found in neoadjuvant IO+C patients compared to the neoadjuvant chemotherapy patients.ConclusionsSleeve lobectomy for advanced NSCLC following IO+C is feasible, although the operations become more complex, neoadjuvant IO+C did not delay postoperative recovery.

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Tumor immune microenvironment predicts the pathologic response of neoadjuvant chemoimmunotherapy in non-small-cell lung cancer.

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Tumor immune microenvironment predicts the pathologic response of neoadjuvant chemoimmunotherapy in non-small-cell lung cancer.

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