Boris I Chobrutskiy1, Saif Zaman1, Andrea Diviney1, Moody M Mihyu1, George Blanck2,3. 1. Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, USA. 2. Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, USA. gblanck@health.usf.edu. 3. Immunology Program, H. Lee Moffitt Cancer Center and Research Institute, 12901 Bruce B. Downs Bd. MDC7, Tampa, FL, 33612, USA. gblanck@health.usf.edu.
Abstract
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.
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.
Entities:
Keywords:
Antigen chemical complementarity; Biochemical features; Bioinformatics; Cancer survival outcomes; T-cell receptor-alpha CDR3
Authors: Brandon J Manley; Philipp M Altrock; Meghan C Ferrall-Fairbanks; Nicholas H Chakiryan; Boris I Chobrutskiy; Youngchul Kim; Jamie K Teer; Anders Berglund; James J Mulé; Michelle Fournier; Erin M Siegel; Jasreman Dhillon; Seyed Shayan A Falasiri; Juan F Arturo; Esther N Katende; George Blanck Journal: Cancer Res Date: 2022-03-01 Impact factor: 12.701
Authors: Brooke E Mcbreairty; Boris I Chobrutskiy; Andrea Chobrutskiy; Etienne C Gozlan; Michael J Diaz; George Blanck Journal: Biomed Rep Date: 2022-06-09
Authors: Jacqueline Wahura Waweru; Kennedy Wanjau Mwangi; Vayda R Barker; Etienne C Gozlan; Michelle Yeagley; George Blanck; Francis W Makokha Journal: J Cancer Res Clin Oncol Date: 2022-09-13 Impact factor: 4.322