细胞毒性 T 淋巴细胞是负责预防癌症的主要效应免疫细胞，因为它们靶向通过癌细胞上的主要组织相容性复合物 (MHC) 呈递的肽新抗原，从而导致细胞死亡。靶向肽-MHC (pMHC) 复合物由于其针对癌症的特异性和有效性，为免疫治疗提供了一种有前途的策略。在这项工作中，我们利用酸性肿瘤微环境，使用 pH（低）插入肽 (pHLIP) 选择性地将抗原肽递送至癌细胞。我们证明，将 MHC 结合肽直接递送至黑色素瘤细胞的细胞质，导致抗原肽在 MHC 上呈递，并随后激活 T 细胞。这项工作强调了 pHLIP 作为抗原肽靶向递送载体的潜力，以及它们通过癌细胞表面 MHC 结合复合物呈递以激活 T 细胞，对增强抗癌免疫治疗具有重要意义。

Cytotoxic T lymphocytes are the primary effector immune cells responsible for protection against cancer, as they target peptide neoantigens presented through the major histocompatibility complex (MHC) on cancer cells, leading to cell death. Targeting peptide-MHC (pMHC) complexes offers a promising strategy for immunotherapy due to its specificity and effectiveness against cancer. In this work, we exploit the acidic tumor micro-environment to selectively deliver antigenic peptides to cancer cells using pH(low) insertion peptides (pHLIP). We demonstrated that the delivery of MHC binding peptides directly to the cytoplasm of melanoma cells resulted in the presentation of antigenic peptides on MHC, and subsequent activation of T cells. This work highlights the potential of pHLIP as a vehicle for targeted delivery of antigenic peptides and their presentation via MHC-bound complexes on cancer cell surfaces for activation of T cells with implications for enhancing anti-cancer immunotherapy.