Abstract PS17-07: Impact of chemotherapy (chemo) on t-cell maturation and clonal proliferation in early-stage and metastatic breast cancer

Background Adaptive immunity is initiated by T-cell receptor (TCR) engagement with cognate tumor antigen, leading to T-cell maturation (i.e. conversion from naive to effector state), clonal proliferation, and potentially tumor elimination. Therefore, broad T-cell repertoire diversity could be an important determinant of anti-tumor immunity. In breast cancer, chemo may facilitate adaptive immunity, but conversely may also be lymphotoxic. We characterize the impacts of curative-intent chemo and palliative combination chemo/immune checkpoint inhibition (ICI) on lymphocyte quantity, maturation, and clonal proliferation. Methods Peripheral blood mononuclear cells (PBMCs) were collected at baseline and serially in stage I-III subjects receiving curative-intent chemo (dose-dense doxorubicin, cyclophosphamide, paclitaxel, n=20), and in stage IV subjects receiving palliative ICI (pembrolizumab) plus chemo (paclitaxel, n=15; or capecitabine, n=14). Flow cytometry was conducted on fresh PBMCs to minimize cellular losses related to cryopreservation. DNA was extracted for T-cell clonality analysis using the immunoSEQ Assay (Adaptive Biotechnologies) at deep resolution. T-cell richness, calculated using the iChao1 richness estimator was used to assess overall T-cell diversity. Results Both dose-dense chemo and palliative chemo/ICI were lymphodepleting, however dose-dense chemo was associated with greater reductions in CD4+ naive T cell count (week 8 counts 34% vs. 96% of baseline, p Citation Format: Brie M Chun, Joanna Pucilowska, Valerie Conrad, Mark Schmidt, Isaac Kim, Paul Fields, Alison Conlin, Heather McArthur, David B Page. Impact of chemotherapy (chemo) on t-cell maturation and clonal proliferation in early-stage and metastatic 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 PS17-07.