Abstract PS4-32: Tim3 expression on tumor infiltrating lymphocytes is associated with poor response to neoadjuvan chemotherapy in patients with locally advanced triple negative breast cancer

Abstract

Abstract Background: Expression of immune checkpoint receptors (ICR) on tumor infiltrating lymphocytes (TILSs) is associated with better response to immunotherapies via immune checkpoint inhibitors. Therefore, we investigated various ICR expressions on TILs in patients with locally advanced triple negative breast cancer (TNBC) after neoadjuvant chemotherapy (NAC). Methods: Expressions of ICRs were examined immunohistochemically by staining surgical specimen (n=61) using specific monoclonal antibodies for PDL-1, PD-1, TIM-3, LAG-3, CTLA-4. Positivity was defined staining >1% on TILs. Results: Median age was 49 (24-76) years. The majority patients were clinically T3-4 (n=31, 50.8%), and clinically N1-3 (n=58, 95.1%) before NAC. Of those, 82% were found to have CTLA-4 positivity, whereas TILs associated positivites for PD1, PDL-1, LAG3 and TIM-3 were 62.3%, 50.9%, 26.2%, 68.9%. High expression of CTLA-4 was found to be associated with a better chemotherapy response (OR=7.94, 95%CI: 0.9-70.12, p=0.06), whereas TIM-3 positivity was contrarly associated with a worse chemotherapy response (OR=0.253, 95%CI: 0.066-0.974, p=0.047) as measured by MDACC Residual Cancer Burden Index. At a 47-month follow-up, patients with ypN0 disease (DFS; HR=0.31, 95% CI: 0.12-0.83, p=0.02 and DSS; HR=0.21, 95% CI:0.07-0.62, p=0.005) and CTLA-4 high expression on TILs (DFS; HR=0.38, 95% CI=0.17-0.85, p=0.019 and DSS; HR=0.34, 95% CI:0.15-0.78, p=0.01) were found to have improved survival. Conclusions: These findings demonstrate that CTLA-4, PD-1, PDL-1 and TIM-3 were highly expressed in TNBC after NAC. Our results more favor an immuncheckpoint inhibitor therapy via CTLA-4 alone or in combination with other immune check point inhibitors against PDL-1 and/or TIM-3 in addition to NAC in advanced TNBC. Citation Format: Neslihan Cabioglu, Semen Onder, Gizem Oner, Hüseyin Karatay, Mustafa Tukenmez, Mahmut Muslumanoglu, Abdullah Igci, Yesim Eralp, Adnan Aydiner, Pinar Saip, Ekrem Yavuz, Vahit Ozmen. Tim3 expression on tumor infiltrating lymphocytes is associated with poor response to neoadjuvan chemotherapy in patients with locally advanced triple negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-32.