RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Immune evasion mechanisms and therapeutic strategies in gastric cancer.
Immune evasion mechanisms and therapeutic strategies in gastric cancer.
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胃癌(GC)是一种高发病率和高死亡率的恶性肿瘤。肿瘤免疫微环境在促进癌症发生和支持GC进展中发挥重要作用。越来越多的证据表明,GC细胞能够发挥多种机制重塑肿瘤免疫微环境并诱导免疫逃逸。在本综述中,我们系统总结了GC细胞与免疫细胞之间复杂的相互作用,包括肿瘤相关巨噬细胞、中性粒细胞、髓源性抑制细胞、NK 细胞、效应T细胞、调节性T细胞和B细胞。
我们重点关注GC细胞如何改变这些免疫细胞,从而创建一个免疫抑制微环境,保护GC细胞免受免疫攻击。最后,我们汇总了基于免疫检查点抑制剂的免疫治疗的最新进展,包括单独使用以及与常规疗法联合使用。抗细胞毒性T淋巴细胞相关蛋白4和抗程序性细胞死亡蛋白1/程序性死亡配体1治疗单独使用并未为GC治疗提供实质性临床获益。
然而,免疫检查点抑制剂与化疗或靶向治疗的联合在难治性和晚期GC患者中展现出有前景的生存优势。本综述提供了对GC免疫逃逸机制的全面理解,并强调了有前景的免疫治疗策略。
Gastric cancer (GC) is a malignancy with a high incidence and mortality. The tumor immune microenvironment plays an important role in promoting cancer development and supports GC progression. Accumulating evidence shows that GC cells can exert versatile mechanisms to remodel the tumor immune microenvironment and induce immune evasion.
In this review, we systematically summarize the intricate crosstalk between GC cells and immune cells, including tumor-associated macrophages, neutrophils, myeloid-derived suppressor cells, natural killer cells, effector T cells, regulatory T cells, and B cells.
We focus on how GC cells alter these immune cells to create an immunosuppressive microenvironment that protects GC cells from immune attack.
We conclude by compiling the latest progression of immune checkpoint inhibitor-based immunotherapies, both alone and in combination with conventional therapies. Anti-cytotoxic T-lymphocyte-associated protein 4 and anti-programmed cell death protein 1/programmed death-ligand 1 therapy alone does not provide substantial clinical benefit for GC treatment.
However, the combination of immune checkpoint inhibitors with chemotherapy or targeted therapy has promising survival advantages in refractory and advanced GC patients. This review provides a comprehensive understanding of the immune evasion mechanisms of GC, and highlights promising immunotherapeutic strategies.
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