Abstract 6661: Profiling response to oncolytic adenovirus and immune checkpoint inhibitors by mass cytometry in a triple negative breast cancer mouse model
Authors: Weidong Xu, Qiaoshan Lin, Yan Li, Beniamin Filimon, Soon Cheon Shin, Michael Olson, Mengjie Chen
Journal: Cancer Research (2024)

Abstract Immune checkpoint inhibitors (ICIs) based immunotherapy has found success in treating breast cancers but for more immunosuppressive cancer types, especially most of triple negative breast cancers (TNBCs), response rates generally are low. Also, combination immunotherapy with oncolytic adenoviruses (OAVs) has been shown to induce a more immune inflamed phenotype in many pre-clinical studies. Here, by using a 40-antibody panel for mass cytometry, we profiled comprehensive changes of cell phenotypes in a TNBC mouse model both systemically and in the tumor microenvironment in response to the treatment of ICIs and/or a new systemically delivered, TGFβ signaling inhibiting OAV, mHAdLyp.sT. The samples in this study were collected on day 16 of tumor cell inoculation, while mHAdLyp.sT were applied by tail vein on day 7 and 9, and anti-PD-1 and anti-CTLA-4 antibodies were injected Intraperitoneally on day 8, 10, 12, 14. After sample processing and data acquisition on Helios system, a standard workflow was applied for data preprocessing including normalization, compensation, transformation, diagnostic analysis, marker ranking, cell population identification, visual representation, differential analysis, and statistical analysis. In blood samples, for T cell clusters, percentages of effector CD8+ T cells, naïve CD8+ T cells, and CD44lowCD62Llow CD8+ T cells among total cells were increased by mHAdLyp.sT, anti-PD-1, and anti-CTLA-4 combination when compared to the buffer group but none of these significant changes were observed in groups treated with mHAdLyp.sT or ICI antibodies alone. Combination treatment also increased percentages of clusters of CD272highCD44high DCs, CD44highCD62Llow B cells, and CD44high macrophages significantly. In spleen, combination treatment significantly increased several T cell clusters, including TCRβhighCD38highRORγthigh T cells, TCRβhigh CD4+ T cells, effector CD8+ T cells, TCRβhighCD44lowCD62Llow CD8+ T cells, and CD11bhigh CD8+ T cells when compared to the buffer group. Interestingly, while ICIs treatment increased several macrophage clusters, such as CD44highLy-6G/Chigh macrophages, CD11blow macrophages, and CD44highCD11bhigh macrophages, they are not significantly increased in the combination treatment group. In the tumor, we did not detect any significant changes by the combination treatment in the clusters we identified now although the average percentages of several clusters were either increased or decreased. We will refine these algorithm-generated clusters from tumors once we obtain our data from day 24 sample collection point for advanced analysis. In short, our current results suggested that the combination therapy is more potent in generating cytotoxic T cells and other anti-tumor immune cell populations systemically in the early stage of the treatment and tumor progression. Citation Format: Weidong Xu, Qiaoshan Lin, Yan Li, Beniamin Filimon, Soon Cheon Shin, Michael Olson, Mengjie Chen. Profiling response to oncolytic adenovirus and immune checkpoint inhibitors by mass cytometry in a triple negative breast cancer mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6661.