T-cell Receptor (TCR) Chemistry And Survival Data Support The Consideration Of ARMC3 As A Breast Cancer Antigen

Abstract

Background Given basic advances in cancer immunotherapy, further understanding of potential antigenic targets will improve treatment protocols. Cancer testes antigens (CTAs) are relatively novel proteins to consider in the overlap of the breast cancer and immunotherapy setting. CTAs are normally expressed in benign testis and placenta; and show aberrant expression in many malignancies, including breast cancer. This work indicated that the CTA, ARMC3 (Armadillo repeat-containing protein 3) is commonly expressed in breast cancer, and when evaluated for its chemical relationship to breast cancer resident T-cell receptor (TCR) chemical features, there was an indication of T-cell response to ARMC3. This result was substantially informed by survival data and granzyme expression. Methods The software used for the recovery of TCR recombination reads is available at https://github.com/bchobrut-USF/blanck_group. TCR alpha and TCR beta recombination data were extracted from the National Institutes of Health (NIH) genomics datasets. Chemical complementarity scores (CSs) were determined using the software available at https://github.com/bchobrut/brca_swcs. Linkage of chemical CSs to survival rates, and to RNAseq values (for assessing gene expression), was done with a web tool designed for these purposes termed, adaptivematch.com. Kaplan-Meier analysis conducted to compare survival probability for the upper and lower 50th percentiles of CSs. Multivariate analysis of age, race, menopause, cancer stage was performed for ARMC3-based CSs. Results Among a set of approximately 280 CTAs, ARMC3 expression stood out as representing a strong distinction for survival rates for both OS and DFS (OS p=0.0147, DFS p=0.0105). We next considered the possibility that a TCR CDR3-ARMC3 interaction would be consistent with the expression of immune biomarkers. Results indicated higher RNA expression of certain immune markers with increasing CS values. There was a survival distinction for the upper and lower 50th percentiles of CSs, with the upper 50th percentile representing a greater disease-free survival probability. Only the tumor stage and the ARMC3 based CS represented independent factors associated with survival distinctions. Conclusion For the ARMC3 expression; the higher the expression level, the better the survival probability. CS assessments of TCR CDR3-CTA pairs may indicate targetable antigens and may be useful for risk stratification and guiding therapy in breast cancer.