Abstract 159P
Background
Increasing evidence suggests a link between T-cell senescence and tumor prognosis. In particular, high levels of circulating senescent T-lymphocytes have been correlated with a worse response to treatment. In this perspective, a therapeutic approach aimed at T-cell senescence clearance is regarded as an innovative strategy 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 BC treated with NAT, according to the different biological subtypes.
Methods
Sixty-nine patients diagnosed with early stage BC candidate to preoperative therapy have been enrolled so far. CD3+ T cells were isolated from peripheral blood (PB) by Ficoll stratification at baseline and after NAT (before surgery). The cyclin-dependent kinase inhibitor (CDKi) p16 was used to characterize T-cell senescence by RT-PCR. RPLP-0 gene was used as housekeeping gene and healthy controls were used for data normalization (2-ΔΔCt). The Mann-Whitney test (Wilcoxon rank sum test) was used to highlight a possible association between p16 expression and response to NAT.
Results
Currently, 48 patients have been tested for T-cell senescence at baseline and after NAT. Of these, 17 (35%) were triple negative (TN), 10 (21%) Luminal and 21 (44%) HER2+. Overall, 26 out to 48 patients (54%) achieved pathological complete response (pCR). No significant difference in p16 relative expression at baseline and after NAT was observed in patients who achieved a pCR: (4.87±1.33 vs 6.01±1.25; p=0.0649). In patients with residual disease (RD), a significant increase in the expression of p16 was observed after NAT (1.76±0.46 vs 5.54±0.85; p=<0.0001).
Conclusions
These preliminary results suggest that the increase of circulating senescent p16-positive T-cells after NAT is correlated with a worse response to treatment. Analyses will be presented according to different biological BC subtypes.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Francesca D'Avanzo.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.