独立遗传筛选结果的秩聚合揭示癌症过继性细胞转移治疗的新策略

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 ( AAK1 N125 , 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.