Abstract 5514: Analysis of immune checkpoint receptor expression by circulating T cells and tumor specimens in patients pre- and post-neoadjuvant chemotherapy for operable breast cancer
Authors: Dionisia M. Quiroga, Andrew Stiff, Christopher McQuinn, Zaibo Li, Hiroaki Nitta, Himanshu Savardekar, Brooke Benner, Bhuvaneswari Ramaswamy, Maryam Lustberg, Rachel Layman, Erin Macrae, Mahmoud Kassem, Nicole Williams, Sagar Sardesai, Jeffrey VanDeusen, Daniel Stover, Mathew Cherian, Thomas Mace, Lianbo Yu, Megan Duggan, William E. Carson, Robert Wesolowski
Journal: Cancer Research (2020)

Abstract While combinations of immune checkpoint (ICP) inhibitors and neo-adjuvant chemotherapy (NAC) have begun to be tested in patients with breast cancer (BC), chemotherapeutic effects on ICP expression in circulating T cells are still unclear. This information could help design future clinical trials including the selection of the best ICP inhibitors to be incorporated into NAC and finding predictive/prognostic biomarkers. Peripheral blood samples and/or tumor specimens before and after NAC were obtained from twenty-four women with operable BC. Using flow cytometry, the expression of CTLA4, PD-1, Lag3, OX40, and Tim3 on circulating T lymphocytes before and at the end of NAC were measured. Differences in the percentage of CD4+ and CD8+ T cells expressing various checkpoint receptors pre- and post-NAC were determined by a paired t-test. This data showed decreased ICP expression after NAC by circulating CD4+ T cells, including significant decreases in CTLA4 (p&amp;lt;0.001), Lag3 (p&amp;lt;0.001), OX40 (p&amp;lt;0.001), and PD-1 (p&amp;lt;0.001). In comparison, circulating CD8+ T cells showed a significant increase in CTLA4 (p&amp;lt;0.003), Lag3 (p=0.001), and OX40 (p&amp;lt;0.001). In comparing breast cancer subtypes, it was found there were significantly lower amounts of circulating Lag3+ CD4+ T cells from triple-negative (lacking estrogen, progesterone, and HER2 receptor expression) breast cancer patients than those from breast cancer patients with tumors expressing at least one of these receptors. Furthermore, using multi-color immunohistochemistry (IHC), the expression of stromal tumor infiltrating lymphocytes (TILs), CD8+ T cells, and PD-1/PD-L1 within the tumor were determined before and after NAC. This analysis revealed fewer tumor specimens were considered to be PD-L1/PD-1 positive post-NAC as compared to pre-NAC biopsy samples using a cutoff of 1% or greater expression. Overall, this work reveals that NAC has opposing effects on ICP expression by CD4+ and CD8+ T cells as well as provides a starting point to study the biological significance of these changes in BC patients.Trial registration: NCT04022616 Citation Format: Dionisia M. Quiroga, Andrew Stiff, Christopher McQuinn, Zaibo Li, Hiroaki Nitta, Himanshu Savardekar, Brooke Benner, Bhuvaneswari Ramaswamy, Maryam Lustberg, Rachel Layman, Erin Macrae, Mahmoud Kassem, Nicole Williams, Sagar Sardesai, Jeffrey VanDeusen, Daniel Stover, Mathew Cherian, Thomas Mace, Lianbo Yu, Megan Duggan, William E. Carson, Robert Wesolowski. Analysis of immune checkpoint receptor expression by circulating T cells and tumor specimens in patients pre- and post-neoadjuvant chemotherapy for operable breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5514.