Chemical Complementarity of Breast Cancer Resident, T-Cell Receptor CDR3 Domains and the Cancer Antigen, ARMC3, is Associated With Higher Levels of Survival and Granzyme Expression
Nagehan Pakasticali, Andrea Chobrutskiy, Dhruv N. Patel, Monica Hsiang, Saif Zaman, Konrad J. Cios, George Blanck, Boris I. Chobrutskiy
Abstract
Introduction: One of the most pressing goals for cancer immunotherapy at this time is the identification of actionable antigens. Methods: This study relies on the following considerations and approaches to identify potential breast cancer antigens: (i) the significant role of the adaptive immune receptor, complementarity determining region-3 (CDR3) in antigen binding, and the existence cancer testis antigens (CTAs); (ii) chemical attractiveness; and (iii) informing the relevance of the integration of items (i) and (ii) with patient outcome and tumor gene expression data. Results: We have assessed CTAs for associations with survival, based on their chemical complementarity with tumor resident T-cell receptor (TCR), CDR3s. Also, we have established gene expression correlations with the high TCR CDR3-CTA chemical complementarities, for Granzyme B, and other immune biomarkers. Conclusions: Overall, for several independent TCR CDR3 breast cancer datasets, the CTA, ARMC3, stood out as a completely novel, candidate antigen based on multiple algorithms with highly consistent approaches. This conclusion was facilitated by use of the recently constructed Adaptive Match web tool.