TIM-3 increase during anti PD-1 treatment is associated with disease progression in patients with non-small cell lung cancer and renal carcinoma

JULIÁ, ESTEFANÍA PAULA; MANDÓ, PABLO; RIZZO, MANGLIO; TSOU, FLORENCIA; LUCA, ROMINA; BRAVO, ALICIA INÉS; ASTORINO, WALTER; MORDOH, JOSÉ; MARTÍN, CLAUDIO; LEVY, ESTRELLA MARIEL

Congreso; Reunión conjunta SAIC-SAI-SAFIS 2018; 2019

Cancer immunotherapies targeting PD-1/PD-L1 axis have shownefficacy in a wide range of cancers. However, not all patients benefitfrom treatment. In a cohort of 18 non-small cell lung cancer (NSCLC)and 7 renal carcinoma (RC) patients, we assessed immunecell populations and soluble mediators in peripheral blood before(PRE) and after (POST) 8-12 weeks of therapy with anti-PD-1 mAbsPembrolizumab or Nivolumab. The aim was to identify potential biomarkersof response.We used an automated hematology analyzer to study white bloodcell counts and flow cytometry to analyze lymphocyte subpopulations(CD4, CD8 and regulatory T cells and NK cells) and markersof activation/differentiation on T cells. Plasmatic C-Reactive Protein (CRP) and cytokine concentration were measured using CRP assayand Cytometric Bead Array, respectively.12 patients presented stable disease or response (SD-R) while 9patients progressed (PD). Response was not evaluable in 4 patients.No differences were observed in any of the markers analyzedin pre-treatment samples between PD and SD-R patients. So wecompared the variation (POST minus PRE median values) of eachmarker between both response groups. Patients with PD, in contrastto SD-R, presented an increase in the percentage of TIM-3+within CD4 (median variation [IQR]: +2.8% [+1.7?+4.1] vs -1.6%[-2.9? -1.2], p=0.0018) and CD8 (+5.5% [+4.0?+6.5] vs -1.9% [-2.3?-0.38], p=0.0009) T cells. PFS analysis showed that increase of TIM-3 expressing cells was deleterious for survival (CD4 p=0.001; CD8p=0.002). Evaluation of soluble mediators? variation showed significantdifferences between PD and SD-R patients in CPR (+9.9mg/lvs -5.9mg/l, p=0.03) and IL-8 (+8.8pg/ml vs -3.1pg/ml, p=0.015)plasma levels.TIM-3 expression in TILs has been previously described as a resistancemechanism to anti-PD-1 therapy. The evaluation of TIM-3 inperipheral blood lymphocytes may be a more accessible and usefultool to monitor progression to this therapy.