Hah Yoon-Soo, Koo Kyo-Chul
Department of Urology, Catholic University of Daegu School of Medicine, Daegu 42472, Korea.
Department of Urology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06229, Korea.
Int J Mol Sci. 2021 Apr 24;22(9):4452. doi: 10.3390/ijms22094452.
Renal cell carcinoma (RCC) is a malignant tumor associated with various tumor microenvironments (TMEs). The immune system is activated by the development of cancer and drives T cell anti-tumor response. CD8 T cells are known to improve clinical outcomes and sensitivity to immunotherapy, and play a crucial role against tumors. In contrast, tumor-associated macrophages (TAMs) suppress immunity against malignancy and lead to tumor progression. TAMs are promoted from damaged TMEs and mount proinflammatory responses to pathogens. Initial immunotherapy consists of interferon-α and interleukin-2. However, response to such therapy is unclear in most patients, and it is associated with high levels of toxicity. Immune checkpoint inhibitors (ICIs), which up-regulate immune responses by blocking the programed cell death protein 1 (PD-1) receptor, the ligand of PD-1, or cytotoxic T-lymphocyte-associated protein 4 T cells, have led to a new era of immunotherapy. Furthermore, combination strategies with ICIs have proven effective through several randomized controlled trials. We expect the next generation of immunotherapy to lead to better outcomes based on ongoing trials and inspire new therapeutic strategies.
肾细胞癌（RCC）是一种与多种肿瘤微环境（TME）相关的恶性肿瘤。免疫系统会因癌症的发展而被激活，并驱动T细胞的抗肿瘤反应。已知CD8 T细胞可改善临床结局并提高对免疫疗法的敏感性，在抗肿瘤过程中发挥关键作用。相比之下，肿瘤相关巨噬细胞（TAM）会抑制针对恶性肿瘤的免疫反应并导致肿瘤进展。TAM由受损的TME促进产生，并对病原体产生促炎反应。初始免疫疗法包括α干扰素和白细胞介素-2。然而，大多数患者对这种疗法的反应尚不清楚，并且它与高水平的毒性相关。免疫检查点抑制剂（ICI）通过阻断程序性细胞死亡蛋白1（PD-1）受体、PD-1配体或细胞毒性T淋巴细胞相关蛋白4 T细胞来上调免疫反应，从而开创了免疫疗法的新时代。此外，ICI联合治疗策略已通过多项随机对照试验证明是有效的。基于正在进行的试验，我们期待下一代免疫疗法能带来更好的结果，并激发新的治疗策略。
