Version 1
: Received: 1 March 2024 / Approved: 1 March 2024 / Online: 4 March 2024 (10:48:06 CET)
How to cite:
Lim, Z.; Wu, X.; Zhu, L.; Albandar, H.; Hafez, M.; Zhao, C.; Almubarak, M.; Smolkin, M.B.; Zheng, H.; Wen, S.; Ma, P.C. Quantitative Peripheral Live Single T-Cell Dynamic Polyfunctionality as a Predictive Biomarker in Cancer Immunotherapy. Preprints2024, 2024030077. https://doi.org/10.20944/preprints202403.0077.v1
Lim, Z.; Wu, X.; Zhu, L.; Albandar, H.; Hafez, M.; Zhao, C.; Almubarak, M.; Smolkin, M.B.; Zheng, H.; Wen, S.; Ma, P.C. Quantitative Peripheral Live Single T-Cell Dynamic Polyfunctionality as a Predictive Biomarker in Cancer Immunotherapy. Preprints 2024, 2024030077. https://doi.org/10.20944/preprints202403.0077.v1
Lim, Z.; Wu, X.; Zhu, L.; Albandar, H.; Hafez, M.; Zhao, C.; Almubarak, M.; Smolkin, M.B.; Zheng, H.; Wen, S.; Ma, P.C. Quantitative Peripheral Live Single T-Cell Dynamic Polyfunctionality as a Predictive Biomarker in Cancer Immunotherapy. Preprints2024, 2024030077. https://doi.org/10.20944/preprints202403.0077.v1
APA Style
Lim, Z., Wu, X., Zhu, L., Albandar, H., Hafez, M., Zhao, C., Almubarak, M., Smolkin, M.B., Zheng, H., Wen, S., & Ma, P.C. (2024). Quantitative Peripheral Live Single T-Cell Dynamic Polyfunctionality as a Predictive Biomarker in Cancer Immunotherapy. Preprints. https://doi.org/10.20944/preprints202403.0077.v1
Chicago/Turabian Style
Lim, Z., Sijin Wen and Patrick C Ma. 2024 "Quantitative Peripheral Live Single T-Cell Dynamic Polyfunctionality as a Predictive Biomarker in Cancer Immunotherapy" Preprints. https://doi.org/10.20944/preprints202403.0077.v1
Abstract
Predictive biomarkers for immune checkpoint inhibitors (ICI), such as PD-L1 expression (TPS), remain limited in clinical applications. Improved novel ICI predictive biomarkers are urgently needed. We evaluated a live single-cell functional liquid biopsy cytokine profiling platform to track immunotherapy treatment response and outcomes. Peripheral blood mononuclear cell samples of healthy donors and NSCLC patients undergoing ICI-based therapies were collected longitudinally pre-/post-treatment under IRB-approved protocols. Samples were enriched for CD4+ and CD8+ T-lymphocytes and analyzed on the IsoLight platform. The single T-cells were captured in microchambers on IsoCode chips for cytokines profiling. Functional polyfunctionality data from 55,775 single cells were analyzed using the IsoSpeak software, kappa coefficient, and Kaplan-Meier survival plots. We found a significant difference between responders and non-responders in CD8+ T-cells’ changes in overall polyfunctionality and polyfunctional strength index (ΔPSI). ΔPSI score in CD8+ T-cells performed better than PD-L1 TPS and, when combined with PD-L1 TPS, strongly correlated with early ICI treatment response with a kappa coefficient of 1.0 (p=0.003). High CD4+ T-cells ΔPSI predicted a strong trend of improved PFS (3.9-fold) and OS (3-fold). In conclusion, single peripheral T-cell polyfunctionality dynamics analysis is a promising liquid biopsy profiling platform as NSCLC ICI predictive biomarker regardless of oncogene-addiction status.
Keywords
cancer immunotherapy; single cell analysis; predictive biomarkers; immune cytokine profiling; polyfunctionality; polyfunctional strength index; lung cancer
Subject
Biology and Life Sciences, Immunology and Microbiology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
