STAT3 down-regulation for IL-2 inducing TIL-A clinical clue for spatial quantitative pathway analysis

Yun Yang; Shuyi Chen; Wenqian Li; Jason Chengwu Duan; Yuan Yuan; Victor S. Xie; Biaoru Li; Yun Yang; Shuyi Chen; Wenqian Li; Jason Chengwu Duan; Yuan Yuan; Victor S. Xie; Biaoru Li

doi:10.3934/Allergy.2024017

AIMS Allergy and Immunology

2024, Volume 8, Issue 4: 283-295. doi: 10.3934/Allergy.2024017

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Research article

STAT3 down-regulation for IL-2 inducing TIL-A clinical clue for spatial quantitative pathway analysis

1.
Guangdong Medical University, Dongguan, Guangdong, 523808, China
2.
Geisinger Commonwealth School of Medicine, Scranton, PA 18840, USA
3.
Department of Chemistry, University of California, Irvine, CA 92697, USA
4.
Computer Science, University of the Pacific, Stockton, CA, USA
5.
Institute of Aging Research, Guangdong Medical University, Dongguan, Guangdong 523808, China
6.
Krieger School of Arts and Sciences, Institution: Johns Hopkins University. Baltimore, MD, 21287. USA
7.
School of Medicine, CWRU, 10900 Euclid Ave, Cleveland, OH 44106 and Senior Faculty of Principal Research Scientist, Department of Pediatrics and GA Cancer Center, Children Hospital at GA, Augusta, GA 30913, USA
† These two authors contributed equally.

Received: 30 June 2024 Revised: 18 November 2024 Accepted: 20 November 2024 Published: 02 December 2024

Tumor-infiltrating lymphocytes (TILs) can be used in two clinical areas: Adoptive cell therapy (ACT) and studying TIL immune properties ex vivo. After we studied ACT for more than thirty years, we are now going to study T-cells' immune properties for personalized immunotherapy. A spatial-quantitative network model can be applied to analyze the immune properties of T-cells and then develop new strategies under a machine learning algorithm. This study utilized STAT3 complex down-regulation for IL-2 inducing cytotoxic T-lymphocyte (CTL) to study T-cell characteristics. After studying spatial-order regulation from the SMAD-STAT3 axis of multiple protein complexes, we focused on a second protein, or STAT3, knockdown for IL-2-inducing CTL. Because machine learning algorithms require a good pathway configuration to mine targeting genes and targeting drugs, the spatial-time quantification network can address the spatial competition of complex proteins binding to downstream proteins/DNA in network analysis. The research demonstrated that STAT3 downregulation can reactivate CTL under a spatial-order quantification network combined with IL2 inducing. After studying the algorithm of a spatial quantitative network under STAT3 downregulation, we can use the spatial-complex configurations to analyze complex regulation in artificial intelligence for future personalized therapy.
Citation: Yun Yang, Shuyi Chen, Wenqian Li, Jason Chengwu Duan, Yuan Yuan, Victor S. Xie, Biaoru Li. STAT3 down-regulation for IL-2 inducing TIL-A clinical clue for spatial quantitative pathway analysis[J]. AIMS Allergy and Immunology, 2024, 8(4): 283-295. doi: 10.3934/Allergy.2024017

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Abstract

Tumor-infiltrating lymphocytes (TILs) can be used in two clinical areas: Adoptive cell therapy (ACT) and studying TIL immune properties ex vivo. After we studied ACT for more than thirty years, we are now going to study T-cells' immune properties for personalized immunotherapy. A spatial-quantitative network model can be applied to analyze the immune properties of T-cells and then develop new strategies under a machine learning algorithm. This study utilized STAT3 complex down-regulation for IL-2 inducing cytotoxic T-lymphocyte (CTL) to study T-cell characteristics. After studying spatial-order regulation from the SMAD-STAT3 axis of multiple protein complexes, we focused on a second protein, or STAT3, knockdown for IL-2-inducing CTL. Because machine learning algorithms require a good pathway configuration to mine targeting genes and targeting drugs, the spatial-time quantification network can address the spatial competition of complex proteins binding to downstream proteins/DNA in network analysis. The research demonstrated that STAT3 downregulation can reactivate CTL under a spatial-order quantification network combined with IL2 inducing. After studying the algorithm of a spatial quantitative network under STAT3 downregulation, we can use the spatial-complex configurations to analyze complex regulation in artificial intelligence for future personalized therapy.

Acknowledgments

Under the support of Dr. H. D. Preisler, we have set up a method to analyze genomic profiles of CD3, CD4, and CD8 from TIL. This work was supported by the National Cancer Institute IRG-91-022-09, USA (to BL). Mentions of trade names or commercial products in this article are solely for the purpose of providing specific information and do not imply recommendation.

Conflict of interest

Biaoru Li is an editorial board member for AIMS Allergy and Immunology and was not involved in the editorial review or the decision to publish this article. All authors declare that there are no competing interests.

Author contributions

YY (1) all papers with references check, VX for ChIP with statistics support and SYC rtPCR and CTL with statistics support. WQL and JD perform data, bioinformatics and biostatistics, YY (5) teaches YY (1) rtPCR and Western blot and VX performs rtPCR and Western blot under BL. BL conceived and designed the experiments.

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