CD8(high)CD57(+) T-cell population as an independent predictor of response to chemoradiation therapy in extensive-stage small cell lung cancer.

Abstract

Tangible clinical benefit is achieved in only a relatively small proportion of extensive-stage small cell lung cancer (SCLC) patients receiving current treatment strategies. Therefore, a more personalized use of current and novel treatment approaches is of critical importance. Individualized therapy relies on the identification of specific biomarkers predictive of response to a particular type of cancer treatment. Immune-related parameters emerge as powerful biomarkers among a variety of predictors of clinical response to various types of cancer treatment. Using multicolor flow cytometry, we evaluated a predictive value of CD8(high)CD57(+) T-cell population and its immunosuppressive (FOXP3(+), NKG2A(+)) and cytotoxic (Perforin(+)) subsets in the peripheral blood of extensive-stage SCLC patients (n=82) treated with either chemotherapy-alone (n=24), or chemoradiation therapy (n=42), or receiving best supportive care (n=16). The low level (<20%) of CD8(high)CD57(+) T cells within the peripheral blood CD8(+) T-cell population and the low level (<3%) of the immunosuppressive FOXP3-positive subset within the CD8(high)CD57(+) T-cell population were independent predictors of a better response to treatment with chemoradiation therapy, but not with chemotherapy alone or best supportive care. Importantly there was no significant survival difference between SCLC patients who were: (i) treated with chemoradiation, but had an unfavourable immune profile (≥20% of CD8(high)CD57(+) T cells and ≥3% of its FOXP3-positive subset), (ii) treated with chemotherapy alone, or (iii) received best supportive care. We show that only a combination of chemotherapy with radiation therapy offered a considerable survival benefit that was confined to a subset of extensive-stage SCLC patients with a favourable predictive immune profile in the peripheral blood.