Optimizing the spatial immune landscape of CD103CD8 tissue-resident memory T cells in non-small cell lung cancer by neoadjuvant chemotherapy.

BACKGROUND

Neoadjuvant chemotherapy (NAC) combined with immunotherapy is increasingly used in non-small cell lung cancer (NSCLC). Tissue-resident memory T (T) cells are the primary subset responding to anti-cancer immunity. However, the immunomodulatory effects of NAC on T cells remain unknown.

METHODS

We established two NSCLC cohorts including patients undergoing upfront surgery (US) and NAC followed by surgery. Beyond the unpaired comparison between the US cohort (n = 122) and NAC cohort (n = 141) with resection samples, 58 matched pre-NAC biopsy samples were available for paired comparisons. Using multiplex immunofluorescence, we characterized T cells (CD103CD8) and four heterogeneous T subsets, including naive T (PD-1Tim-3), pre-exhausted T (PD-1Tim-3), T (PD-1Tim-3), and terminally exhausted T (PD-1Tim-3). Cell density, cytotoxicity, and two spatial features were defined to evaluate the effect of NAC on T subsets.

RESULTS

The cell densities, infiltration scores, and cancer-cell proximity scores of T cells, especially T subsets, were significantly increased after NAC and associated with better prognosis of patients. In Contrast, no significant change was observed in the T subset, which was associated with poor prognosis. Besides, the cytotoxicity of T subsets was unaltered after NAC. Compared with patients without major pathologic response (MPRs), patients with MPR had higher densities of T subsets and higher cancer-cell proximity scores of T subsets. Furthermore, increased density of CD31 + cancer microvessels was positively associated with both T and T cells after NAC.

CONCLUSIONS

NAC may remodel the cell density and spatial distribution of T subsets, which is associated with favorable therapeutic effect and prognosis in patients with NSCLC.