Exploration of Immunology

Table 1. Key challenges and strategies in TIL-based therapies.

Challenge	Description	Potential solution
TIL heterogeneity	Diverse population with varying anti-tumor and immunosuppressive roles	Single-cell technologies of subset identification and enrichment
T cell exhaustion	Reduced effector function due to chronic antigen exposure	Epigenetic reprogramming to reverse exhaustion markers
Tumor microenvironment	Suppressive factors like TGF-β and hypoxia inhibit TIL activity	Genetic engineering for resistance to suppressive signals
Low TIL expansion rates	Insufficient TIL numbers after ex vivo culture	Optimized expansion protocol using cytokines and co-stimulants
Loss of persistence in vivo	Rapid TIL depletion post infusion	Engineering for enhanced persistence and memory-like phenotypes

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TIL: tumor-infiltrating lymphocyte.

Declarations

Acknowledgments

We thank Saveetha University and our respective guides and co-guides for their continued support and feedback during the preparation of this manuscript.

Author contributions

CK: Conceptualization, Methodology, Investigation, Formal analysis, Data curation, Visualization, Writing—original draft. RV: Methodology, Writing—review & editing. AS: Writing—review & editing. VVP: Conceptualization, Supervision, Project administration, Writing—review & editing. All authors read and approved the final manuscript.

Conflicts of interest

The authors declare that they have no competing interests.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

All the data discussed is publicly available from cited repositories, such as GEO and TCGA.

Funding

This research received no specific grant from any funding agency, commercial entity, or not-for-profit organization. The authors declare that they did not receive any financial support for the preparation of this article.

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