Immunomonitoring of anti-PD-1 therapy in renal and non-small cell lung cancer patients

JULIÁ, ESTEFANÍA PAULA; TSOU, FLORENCIA; RIZZO, MANGLIO; LUCA, ROMINA; MANDÓ, PABLO; PÉREZ DE LA PUENTE, CONSTANZA; ASTORINO, WALTER; BRAVO, ALICIA INÉS; MARTÍN, CLAUDIO; LEVY, ESTRELLA MARIEL

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA; SOCIEDAD ARGENTINA DE INVESTIGACIÓN BIOQUÍMICA Y BIOLOGÍA MOLECULAR; SOCIEDAD ARGENTINA DE INMUNOLOGÍA;

Programmed cell death 1 (PD-1) is an inhibitory receptor expressedby exhausted T cells in chronic infections and cancer. Therapies that block the PD-1 pathway have shown promising clinicalresults in a significant number of advanced-stage cancer patients(pts), including non?small cell lung cancer (NSCLC) and renal cellcarcinoma (RCC). Pre-existing T-cell infiltration and/or expressionof PD-L1 in tumors may be used as indicators of clinical response;however, peripheral blood (PB) analysis directed to understand themechanisms of PD-1 blockade has not been extensively studied.Until now, we have analyzed PB samples from 11 advancedstage NSCLC and 4 RCC pts before (PRE) and after 11 weeks(range=8-13) of receiving PD-1?targeted therapies Pembrolizumabor Nivolumab (POST). We use an automated hematology analyzerto study white blood cell counts, and flow cytometry to analyzelymphocyte subpopulations (CD3+, CD8+ and CD4+ T cells, T regulatoryand NK cells) and markers of activation/differentiation on Tcells (CD69, PD-1, TIM-3, ICOS, CCR7, CD45RO and CD95). Ptswere classified according to clinical response in responders (n=4)if presented complete or partial response, stable disease (n=2) orprogressive disease (PD, n=9).We have performed a preliminary analysis on this small cohort ofpts. Pts with PD showed an increase neutrophil-to-lymphocyte ratioafter treatment (Median [IQR]: PRE 3.2 [2.9-3.6] vs POST 9.1 [4.4-12.6]) while this ratio decreased in responder pts (PRE 6.0 [3.6-18]vs POST 2.5 [2.2-3.0]). The same tendency was observed for leukocytecount, neutrophil absolute and relative number, and percentageof TIM-3+ cells within CD8+ T cells.Promising early data suggest that there is an association betweenclinical responses and immunological changes in PB, which mightprovide a better understanding of patients? responses to PD-1?targetedtherapies. Patient recruitment is still ongoing, and circulatinglevels of inflammatory markers will also be studied.