Abstract 49P
Background
Small cell lung cancer (SCLC) is a lethal neoplasia. Addition of anti-PD-L1 immunotherapy (IT) to chemotherapy (CT) has shown modest improvement, may be due to the absence of biomarkers for response and consequent suboptimal selection of patients in clinical trials. As biopsy material is usually scarce and invasively obtained, peripheral immune cells seem an explorable non-invasive source for biomarkers. Here, we identified peripheral immune subsets that predicts durable clinical response (DCR) in SCLC.
Methods
SCLC patients who were candidates for receiving CT plus anti-PD-L1 IT were identified at diagnosis and prospectively recruited. Blood samples were obtained and peripheral blood mononuclear cells (PBMC) isolated prior to administration of the first dose of anti-PD-L1 IT. Markers for proliferation, exhaustion, senescence, adhesion, and immunosuppression were determined by spectral flow cytometry. Cox regression identified the best cut-off for DCR; Wilcoxon test was used for comparisons between groups; A P-value <0.01 was considered statistically significant.
Results
We included 20 newly diagnosed SCLC patients. DCR was defined as >200 days of progression free survival. Non-DCR group comprised 17 patients (85%), while 3 patients (15%) showed DCR. Males were 82% in the non-DCR and 66% in the DCR group. The median age was 67.5 and 60.7 years, while stage III-IV represented 94.1% and 100% respectively. We found that DCR patients show consistent increased proportions of Ki67 expression in CD4+CXCR5+ cells when compared to the non-DCR group (P=0.005). This phenotype corresponds to proliferative follicular helper T cells. Moreover, Ki67 also showed as a predictor marker in those CD8 T cells expressing the co-stimulatory molecule ICOS, as well as in co-expression with the co-receptor TIM-3 (P=0.0018 and 0.0077 respectively).
Conclusions
Proliferative follicular helper T cells (CD4+CXCR5+Ki67+), ICOS+ and TIM-3 cytotoxic T cells (CD8+ICOS+Ki67+; CD8+TIM-3+Ki67+) in peripheral blood predicts DCR to anti-PD-L1 IT in SCLC through a non-invasive routine technique. Determination of these peripheral immune subsets may help to identify those patients who benefit the most from the addition of anti-PD-L1 IT to standard CT.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.