Abstract P2-07-06: Peripheral T-lymphocytes senescence and response to neoadjuvant therapy (NAT) in operable breast cancer (BC)
Authors: Martini Veronica , Saggia Chiara , D'Avanzo Francesca , Rossi Valentina , Dodaro Ivan , Gallarotti Eleonora , Pretato Tania , Varughese Feba Mariam , Vachanaram Ajay Ram , Cavalleri Martina , Stella Arianna , Gobbato Simone , Tassone Andrea , Gambaro Anna , Branni Carmen , Maggiora Paola Maria , Rua Alessia , Boldorini Renzo , Ferrara Eleonora , Krengli Marco , Gennari Alessandra 
Published: March 2022

Abstract
Background: Increasing evidence suggests a link between T-cell senescence and tumour prognosis. In particular, high levels of circulating senescent T-lymphocytes have been also correlated with a worse response to anti-cancer treatments. In this perspective, a therapeutic approach aimed at T-cell senescence clearance and restoring is regarded as an innovative strategy in cancer treatment and is currently under investigation in pre-clinical and clinical models. The purpose of the present study is to characterize the impact of T-cell senescence as a predictive factor of response in patients with operable breast cancer (BC) treated with NeoAdjuvant Therapy (NAT), according to biological subtypes. Methods: Fifty-four patients have been enrolled so far. CD3+ T cells were isolated from peripheral blood (PB) by Ficoll stratification at baseline, before start of treatment, and after NAT, before surgery. The relative expression of two cyclin-dependent kinase inhibitors (CDKi) p16 and/or p21 was used to characterize T-cell senescence, by RT-qPCR. RPLP-0 gene was used as housekeeping gene and data were normalized on normal controls (2-ΔΔCt). Association with type of response to NAT was performed by using the Wilcoxon signed-rank test. Results: At baseline, 19 patients have been tested for T-cell senescence so far: of these, 7 (37%) were Triple Negative (TN), 8 (42%) Luminal B and 4 (21%) HER2+. A higher expression of p16 and p21 was observed in TN BC versus Luminal B and HER2+. p16: 2.78±6.87 vs 1.21±2.10 vs 0.09±0.07 (p=0.05); p21: 2.09±2.79 vs 1.58±1.95 vs 0.86±0.61 (p=0.63). At present surgery has been performed in 16 patients, with an overall pCR rate of 56% (9/16). Patients with a pCR after NAT had a significantly lower expression of p16 at baseline as compared to patients with residual disease: 0.87±2.006 vs 3.07±6.76; p=0.02. Conversely, p21 expression level was not significantly associated: 1.42±1.00 vs 0,81±0.41; p=0.29). Expression of p16 and p21 was assessed in 13 patients at baseline and after the end of NAT, before surgery: overall, p16 expression resulted significantly increased from baseline to end of treatment (p=0,01), whereas p21 did not show the same trend (p=0.13). Conclusions: These preliminary results suggest that the presence of circulating senescent T cells, identified by a p16 low expression level, might represent a novel biomarker to identify those patients with operable BC who are most likely to achieve a pCR at NAT. Updated analyses will be presented.
Citation Format: Veronica Martini, Chiara Saggia, Francesca D'Avanzo, Valentina Rossi, Ivan Dodaro, Eleonora Gallarotti, Tania Pretato, Feba Mariam Varughese, Ajay Ram Vachanaram, Martina Cavalleri, Arianna Stella, Simone Gobbato, Andrea Tassone, Anna Gambaro, Carmen Branni, Paola Maria Maggiora, Alessia Rua, Renzo Boldorini, Eleonora Ferrara, Marco Krengli, Alessandra Gennari. Peripheral T-lymphocytes senescence and response to neoadjuvant therapy (NAT) in operable breast cancer (BC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-07-06.