肿瘤细胞治疗研究
英文原题：Anti-TNFR2 antibody and HMGN1 combined with TIL cell therapy inhibits colorectal cancer progression by enhancing immune response.
Anti-TNFR2 antibody and HMGN1 combined with TIL cell therapy inhibits colorectal cancer progression by enhancing immune response.
抗 TNFR2 抗体与 HMGN1 疗法的联合治疗通过减少肿瘤浸润调节性 T 细胞（Treg 细胞）来协同缓解免疫抑制。
背景：TIL（肿瘤浸润淋巴细胞）免疫疗法治疗多种实体瘤显示出卓越疗效。然而，现有流程通常需要环磷酰胺淋巴细胞清除化疗及大剂量IL-2，以支持回输TIL的增殖和活性，但全身毒性很常见。方法：本研究建立CT26结直肠癌小鼠模型，切除肿瘤组织并分离TIL，在体外培养后通过流式细胞术验证其身份。小鼠接受抗TNFR2抗体、HMGN1和TIL治疗，以评估这一新型免疫联合疗法的抗肿瘤效果。采用流式细胞术分析CD8⁺ T细胞、CD4⁺ T细胞和Treg细胞，并通过CCK-8实验评估TIL功能。结果：给予抗TNFR2抗体和HMGN1不仅刺激TIL增殖，还抑制肿瘤组织内Treg细胞，从而显著增强小鼠TIL介导的抗肿瘤活性。接受该联合治疗的小鼠肿瘤完全清除，生存期显著延长。该免疫联合疗法在4T1乳腺癌小鼠模型中也显示出显著抑瘤作用。结论：抗TNFR2抗体联合HMGN1治疗可通过减少肿瘤浸润调节性T细胞（Treg），协同缓解免疫抑制。Treg减少后，TIL功能和扩增得到促进，从而成功在体内清除肿瘤。
BACKGROUND: Immunotherapy utilizing tumor-infiltrating lymphocytes (TILs) has demonstrated exceptional effectiveness in the treatment of diverse solid tumors. However, existing procedures typically involve lymphodepleting chemotherapy using cyclophosphamide and high-dose IL-2 to support the proliferation and activity of reintroduced TILs, despite the common occurrence of systemic toxicity. METHODS: A CT26 colorectal cancer mouse model was established in this research. Tumor tissues were removed, and TILs were isolated and cultured in vitro. The TIL identity was validated via flow cytometry. Mice received treatment with an anti-TNFR2 antibody, HMGN1, and TILs to assess the effectiveness of this new immune-combination therapy against tumors. Flow cytometry was employed to analyze CD8 + T cells, CD4 + T cells, and Treg cells, with TIL function evaluated using CCK8 assays. RESULTS: Administration of anti-TNFR2 antibody and HMGN1 not only stimulated TIL proliferation but also suppressed Treg cells within tumor tissues, thereby markedly enhancing TIL-mediated anti-tumor activity in mice. Mice receiving this combination therapy achieved complete tumor eradication and significantly prolonged survival. This immune-combination therapy also demonstrated substantial tumor suppression in the 4T1 breast cancer mouse model. CONCLUSION: The combined treatment of the anti-TNFR2 antibody and HMGN1 therapy synergistically alleviates immunosuppression by decreasing tumor-infiltrating regulatory T cells (Treg cells). This decrease in Treg cells results in the successful eradication of tumors in vivo by promoting the function and expansion of TIL.
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