Abstract
Efficient intratumoral infiltration of adoptively transferred cells is a significant barrier to effectively treating solid tumors with adoptive cellular transfer (ACT) therapies. Our recent forward genetic, whole-genome screen identified T cell-intrinsic gene candidates that may improve tumor infiltration of T cells. Here, results are combined with five independent genetic screens using rank aggregation to improve rigor. This resulted in a combined total of 1,523 candidate genes – including 1,464 genes not currently being evaluated as therapeutic targets - that may improve tumor infiltration of T cells. Gene set enrichment analysis of a published human dataset shows that these gene candidates are differentially expressed in tumor infiltrating compared to circulating T cells, supporting translational potential. Importantly, adoptive transfer of T cells overexpressing gain-of-function candidates (AAK1ΔN125, SPRR1B, and EHHADH) into tumor-bearing mice resulted in increased T cell infiltration into tumors. These novel gene candidates may be considered as potential therapeutic candidates that can aid adoptive cellular therapy in improving T cell infiltration into solid tumors.
Original language | English (US) |
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Article number | 1235131 |
Journal | Frontiers in immunology |
Volume | 14 |
DOIs | |
State | Published - 2023 |
Keywords
- adoptive transfer therapy
- cancer immunotherapy
- CAR-T
- Sleeping Beauty
- T cell trafficking
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology