Infiltration of metastatic lymph nodes with PD-1 T cells is associated with improved disease-free and overall survival in resected N NSCLC.

Tumor metastases to regional lymph nodes are associated with worse outcome for patients with resected non-small cell lung cancer (NSCLC), but there is a wide variation in survival. We hypothesized that infiltration of tumor-involved lymph nodes with activated effector T cells would impact subsequent outcome. A total of 54 lymph nodes (27 N and 15 N collected from 12 patients with Stage IIB (TNM) and 12 N lymph nodes collected from 10 patients with Stage IIA (TNM) who underwent lymphadenectomy during surgical management of their NSCLC) were analyzed for effector T cells expressing activation markers PD-1 and TIM-3 using the -multiple immunofluorescence assay. The frequency of CD3CD8 (P=0.0001), CD3CD8TIM-3 (P<0.0001), and CD3CD8TIM-3Ki-67 (P<0.0001) T cells was greater in lymph nodes of IIA patients compared with IIB patients; however the frequency of CD3CD8PD-1 (P=0.0086), CD3CD8TIM-3 (P=0.0129), CD3CD8PD-1Ki-67 (P<0.0001) and CD3CD8TIM-3Ki-67 (P=0.0001) T cells was greater among the tumor involved (N) nodes of N1 patients compared with the tumor-uninvolved (N) nodes. The frequency of intranodal CD3CD8, CD3CD8PD-1 and CD3CD8PD-1Ki-67 T cells in N nodes was associated with prolonged progression-free (PFS) and overall survival (OS). These data suggest that CD3CD8TIM-3 T cells may suppress tumor spread to regional lymph nodes but once tumor cells metastasize to lymph nodes, CD3/CD8/PD-1/Ki67 T cells localizing to N nodes may prevent further tumor spread, resulting in prolonged survival.