Repurposing TRM for tumor immunotherapy

翻译后摘要：重新利用TRM肿瘤免疫治疗 克服免疫抑制肿瘤微环境并定位过继细胞和检查点 对实体瘤的阻断疗法仍然是成功的癌症免疫疗法的主要障碍。这 提案针对这些问题。初步数据表明，人类肿瘤中存在抗病毒T细胞， 细胞在局部识别免疫刺激后仍然有能力触发免疫刺激感测和警报功能， 同源肽。在小鼠中，肽警报疗法与PD-L1协同清除肿瘤， 在没有进一步治疗的情况下，在替代的解剖部位防止肿瘤生长。这项建议 将剖析肽报警治疗触发肿瘤清除的机制，并建立系统的 肿瘤特异性免疫它将测试与其他免疫疗法的协同作用。警方将进一步调查 在人肿瘤外植体上重现肽报警治疗的能力，预期告知临床 审判这一提议可能会对该领域产生持续的影响，因为它定义了癌症免疫治疗的新途径。 它独立运作，但与其他疗法协同作用。

Abstract: Repurposing TRM for tumor immunotherapy Overcoming the immunosuppressive tumor microenvironment and localizing adoptive cell and checkpoint blockade therapies to solid tumors remain major impediments to successful cancer immunotherapy. This proposal addresses these issues. Preliminary data indicates that human tumors are populated with antiviral T cells that remain competent to trigger immunostimulatory sensing and alarm function upon local recognition of cognate peptide. In mice, peptide alarm therapy synergizes with PD-L1 to clear tumors and mice are durably protected against tumor growth at alternative anatomic sites in the absence of further treatment. This proposal will dissect the mechanisms by which peptide alarm therapy triggers tumor clearance and establishes systemic tumor-specific immunity. It will test synergy with other immunotherapies. Further investigations will be made on the ability to recapitulate peptide alarm therapy on human tumor explants in anticipation of informing a clinical trial. This proposal may have a sustained impact on the field by defining a new avenue of cancer immunotherapy that operates independently but synergizes with other therapies.