Abstract 1317: Biomarker evaluation for PD-1 targeted therapies in non-small cell lung cancer (NSCLC) patients

Sustained expression of programmed cell death (PD)-1 inhibitory receptor is a hallmark of exhausted T cells during chronic infections and cancer. PD-1 signaling inhibits T cell activation, and maintains T cells in a dysfunctional state. Notably, inhibition of PD-1 interactions with PD-L1 is able to restore function in exhausted T cells. Several clinical trials have now shown that PD-1 blockade therapy results in durable clinical benefits in advanced stage cancer patients refractory to other treatments, and efficacy has been reported in multiple tumor types. Nonetheless many patients do not respond to PD-1 targeted therapies, hence a better understanding of the immunological responses induced by PD-1 pathway blockade and identification of predictive biomarkers is imperative. In this ongoing study we have analyzed peripheral blood mononuclear cells (PBMC) from advanced stage NSCLC patients, before and during the course of PD-1 pathway blockade therapy. We find that CD8 T cell activation is observed in some patients following therapy, but it is not consistently associated with clinical response. Interestingly, treatment-induced CD8 T cell proliferation is not sustained in some patients even with continuation of therapy. After PD-1 pathway blockade, we find co-expression of CTLA-4 on proliferating PD-1+ CD8 T cells in the blood. Accordingly, we found that tumor infiltrating CD8 T cells expressing high levels of PD-1 also co-express CTLA-4 (and Tim-3) in surgical specimens of patients with NSCLC. We will present additional data on CD8 and CD4 T cells in NSCLC patients enrolled in PD-1 targeted therapies clinical trials and discuss potential biomarkers. We conclude that peripheral blood analysis can provide valuable insights into anti-cancer effects of PD-1 targeted therapy. Citation Format: Alice O. Kamphorst, Rathi N. Pillai, Shu Yang, Rama Akondy, Lydia Koenig, Ke Yu, Megan McCausland, Gabriel Sica, Fadlo R. Khuri, Taofeek K. Owonikoko, Suresh S. Ramalingam, Rafi Ahmed. Biomarker evaluation for PD-1 targeted therapies in non-small cell lung cancer (NSCLC) patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1317. doi:10.1158/1538-7445.AM2015-1317