Combinatorial analysis of CD4+Tregs and CD8+Teff to predict response to ICI in patients with ES-SCLC.

person Konstantinos Tsapakidis Department of Medical Oncology, University Hospital of Larissa, Larissa, Greece info_outline Konstantinos Tsapakidis, Anastasia Xagara, Alexandros Kokkalis, Alexandra Markou, Chrysovalantis Aidarinis, Alexandros Lazarou, Galatea Kallergi, Vasileios Papadopoulos, Emmanouil S. Saloustros, Ioannis Samaras, Athanasios Kotsakis

Authors person Konstantinos Tsapakidis Department of Medical Oncology, University Hospital of Larissa, Larissa, Greece info_outline Konstantinos Tsapakidis, Anastasia Xagara, Alexandros Kokkalis, Alexandra Markou, Chrysovalantis Aidarinis, Alexandros Lazarou, Galatea Kallergi, Vasileios Papadopoulos, Emmanouil S. Saloustros, Ioannis Samaras, Athanasios Kotsakis Organizations Department of Medical Oncology, University Hospital of Larissa, Larissa, Greece, Laboratory of Oncology, School of Health Sciences, University οf Thessaly, Larissa, Greece, Laboratory of Biochemistry/Metastatic Signaling, Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras, Patras, Greece Abstract Disclosures Research Funding No funding received None. Background: Recently, the antiPD-L1 agent, durvalumab, was approved in first line treatment in combination with chemo. However, there is not a clear benefit from this regimen for the majority of patients. In this study, we explored the predictive role of regulatory T-cells in response of patients with ES-SCLC treated with the aforementioned regimen. Moreover, we evaluated the potential role of inflammatory hematological indices such as Neutrophil to Lymphocyte ratio (NLR) and CRP levels to predict responders. Methods: Blood was collected before initiation of immunotherapy from 24 patients with ES-SCLC. PBMCs were isolated with Ficoll density gradient centrifugation from patients and 1O healthy donors (HD). Immunophenotyping was performed by multi-color flow cytometry using antibodies against CD3,CD8,CD45RA,CD45RO,CCR7,PD-1, for CD8 T-cells and CD3,CD4,FoxP3,CD25,CD127,CTLA-4,CD39 for Tregs. Results: High percentages of CD39+ (p = 0.0061) and CTLA-4+ (p = 0.012) Tregs were detected in circulation of ES-SCLC compared to healthy individuals. Additionally, higher percentages of CD8+ Teff were detected in SCLC patients (p = 0.027). Patients with high numbers of Teff had significant higher PFS (p = 0.021, median 183 and 97 days) and better OS (p = 0.075, median 318 and 202 days) in response to immunotherapy compared to those with low numbers. Spearman analysis revealed a significant negative correlation between Tregs and Teff (Spearman r 2 = -0.39,p = 0.043) that was accompanied with significant higher PFS (p = 0.041, median 207 and 130 days ) and OS (p = 0.029, median 318 and 202 days ) in patients with high levels of Teff and low Tregs comparing to the rest. Further analysis on inflammatory clinical signatures demonstrated that patients with better clinical response to immunotherapy have significantly lower NLR (p = 0.034) while no significant difference was revealed for CRP (p = 0.401) levels before therapy initiation. Conclusions: Combinatorial analysis of Tregs and Teff cells may be used as a predictive tool for response to immunotherapy in ES-SCLC patients.