TCF-1+ PD-1+ CD8+T Cells Are Associated With The Response To PD-1 Blockade In Non-Small Cell Lung Cancer Patients

Abstract

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 fifteen advanced NSCLC patients who underwent PD-1 immunotherapy or combined with chemotherapies were analyzed. The frequency of TCF-1+ cells in PD-1+ CD8+T cells were determined in these biospecimens by using multi-label immunofluorescence staining and multi-spectral acquisition technology. The clinical role of TCF-1+PD-1+CD8+T cells were evaluated via analyzing our patients’ clinic parameters and public NSCLC database. Results: A high frequency of TCF-1+ PD-1+ CD8+T cells were identified in responders compared with non-responders (p=0.0427), 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, gender, smoking history, pathologic type and genetic status. In univariate logistic regression analysis, high frequency of TCF-1+ PD-1+ CD8+T cells were significantly correlated with patients’ benefit of PD-1 blockade (p=0.035). 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.

The CX3CL1-CX3CR1 chemokine axis can contribute to tumor immune evasion and blockade with a novel CX3CR1 monoclonal antibody enhances response to anti-PD-1 immunotherapy

“…The progenitor CD8 TIL population, as defined by TCF1+PD-1+, is the population that expands in response to anti-PD-1, and some can convert to a terminally exhausted PD-1+TIM-3+ CD8+ population ( 60 ). The progenitor CD8 TIL were reported to be higher in responders to anti-PD-1 ( 61 ). We examined the PD-1+ TCF1+ and PD-1+TIM-3+ CD8 TIL populations on day 12 after two antibody treatments and saw a trend towards an increase in the PD-1+TCF1+ CD8+ cells in the CX3CR1 mAb and PD-1 mAb+ CX3CR1 mAb treatment groups compared with single agent anti-PD-1 group.…”