TCF-1+ PD-1+ CD8+T cells are associated with the response to PD-1 blockade in non-small cell lung cancer patients

Purpose To determine whether TCF-1(+)PD-1(+)CD8(+)T cells are associated with the response to PD-1 blockade in non-small cell lung cancer (NSCLC) patients. Methods We investigated the expression of TCF-1(+)PD-1(+)CD8(+)T cells and elucidated their predictive role in NSCLC patients. Pretreatment specimens from 20 advanced NSCLC patients who underwent PD-1 immunotherapy or combined with chemotherapy were analyzed. The frequencies of TCF-1(+) cells in PD-1(+)CD8(+)T cells were determined in these biospecimens using multi-label immunofluorescence staining and multi-spectral acquisition technology. The clinical roles of TCF-1(+)PD-1(+)CD8(+)T cells were assessed via analyzing our cases and human NSCLC data collected from public databases. Results A high frequency of TCF-1(+)PD-1(+)CD8(+)T cells was identified in responders compared with non-responders (p = 0.0024), and the patients with high expression of this cell subset had durable clinical benefit of anti-PD-1 therapy. There were no significant association between the expression of TCF-1(+)PD-1(+)CD8(+)T cells and patients' age, smoking history, pathologic type, and genetic status. In univariate analysis by the Cox hazard model, high frequency of TCF-1(+) PD-1(+) CD8(+)T cells was significantly correlated with patients' benefit of PD-1 blockade (p = 0.024). Conclusion Our study indicated that TCF-1(+)PD-1(+)CD8(+)T cells are associated with the response to PD-1 blockade, and may be a predictor of anti-PD-1 therapy.