Abstract
Tumor-infiltrating lymphocytes (TIL), which include tumor-specific T lymphocytes with frequency, are used for adoptive cell transfer therapy (ACT) in clinical practice. The optimization of TIL preparation has been investigated to reduce the senescence and increase the abundance of TIL, as both the quality and quantity of the transferred cells have great influence on the outcome of TIL-based ACT (TIL-ACT). Considering the effects of cell reprogramming on senescence, we expected that the anti-tumor effect could be enhanced by TIL regeneration. To confirm this hypothesis, we established tumor-specific TIL-derived iPS cells (TIL-iPSC) with human colorectal cancer specimens. T cells differentiated from TIL-iPSC (TIL-iPS-T) retained not only intrinsic T cell functions and tumor specificity, but also exhibited improved proliferation capacity and additional killing activity. Moreover, less differentiated profiles and prolonged persistency were seen in TIL-iPS-T compared with primary cells. Our findings imply that iPSC technology has great potential for TIL-ACT.
Highlights
Tumor-infiltrating lymphocytes (TIL), which include tumor-specific T lymphocytes with frequency, are used for adoptive cell transfer therapy (ACT) in clinical practice
TI-cytotoxic T lymphocytes (CTL) expansion was needed before the tumor-specific tumor-infiltrating CTL (TI-CTL) selection phase
Because T-cell receptor (TCR) rearrangement is triggered with recombination activating gene (RAG) during the DP stage, we focused on RAG1 and RAG2 expressions in DP cells from both protocols but found no obvious difference (Supplementary Fig. 5b)
Summary
Tumor-infiltrating lymphocytes (TIL), which include tumor-specific T lymphocytes with frequency, are used for adoptive cell transfer therapy (ACT) in clinical practice. Considering the effects of cell reprogramming on senescence, we expected that the anti-tumor effect could be enhanced by TIL regeneration. To confirm this hypothesis, we established tumor-specific TIL-derived iPS cells (TIL-iPSC) with human colorectal cancer specimens. These tumor-specific T cells mainly recognize neoantigens resulting from somatic mutations in cancer cells For this reason, the mutation profiles are important to determine the efficacy of TIL-based cancer immunotherapy. IPSC technology enables an unlimited supply of antigen-specific CD8+ T cells These advantages regarding T-cell regeneration from T-iPSC have implications for conventional TIL-ACT
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