T-cell receptor-α CDR3 domain chemical features correlate with survival rates in bladder cancer

Purpose: In certain cancer settings, a T-cell response to cancer represents a relatively favorable outcome. Thus, the near-future challenges include a better understanding of exactly which T-cell features contribute to a response to which cancer antigen-groups, to maximize the opportunities for tumor-infiltrating lymphocyte (TIL)-based therapies and other immunotherapies.

Methods: The immune receptor complementarity determining region-3 (CDR3) is considered to be important for antigen binding, hence, in this report, we evaluated the chemical features of the CDR3 of 846 T-cell receptor-α (TCR-α) coding regions associated with bladder tumor tissue, using bioinformatics databases.

Results: Results indicated that statistically significantly distinct, low value, CDR3 region isoelectric points associate with a better outcome (log rank p < 0.027, overall survival). Moreover, in samples representing the more favorable isoelectric points, known driver mutations, for example, PIK3CA (E → K) with chemically complementary features overlap the better-outcome, low isoelectric point samples. Further work extended these results, i.e., survival rate-CDR3 associations, to other CDR3 chemical features and other cancers, consistent with the initial isoelectric point-related, bladder cancer findings.

Conclusions: A bioinformatics assessment of cancer-associated TCR biochemical features may improve the accuracy of the predictions of which TILs will be best for ex-vivo amplification and which patients will benefit from other immunotherapies.