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

The clinical outcome of resectable non-small cell lung cancer (NSCLC) patients receiving neoadjuvant chemoimmunotherapy was great but varies greatly. Meanwhile, 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 have 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. A total of 29 patients with stage 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 major pathological response (MPR) and 41% (12/29) of patients had complete pathological response (pCR). In stroma area of 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 tumor area, the higher infiltration of CD8 + TILs were more likely to appear in patients with non-MPR. In 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 stroma and tumor area. Neoadjuvant chemoimmunotherapy achieved a MPR rate of 55% and induced greater immune infiltration. Besides, we observed that the baseline TILs and its spatial distribution correlates to pathological response.