结直肠癌患者免疫耐药与肿瘤微环境的相关研究进展

Research progress on the relationship between immune resistance and tumor microenvironment in patients with colorectal cancer

结直肠癌(colorectal cancer,CRC)作为世界第三大恶性肿瘤,给社会造成了极大的健康经济负担。近些年来,由免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)发挥主导作用的免疫治疗取得了较大进展。ICIs对微卫星高度不稳定性(microsatellite instability-high,MSI-H)或错配修复缺陷(deficiency of mismatch repair,dMMR)转移性结直肠癌(metastatic colorectal cancer,mCRC)患者效果显著,这为mCRC患者提供了新的治疗方向。即使ICIs在dMMR/MSI-H亚型的mCRC患者中取得了显著的治疗效果,但就总体CRC人群而言,能够从ICIs中获益的仅占少部分,表明存在原发性免疫耐药;此外,初始ICIs治疗获益的患者在治疗过程中可能出现继发性免疫耐药,最终可能导致疾病进展。肿瘤组织与肿瘤微环境(tumor microenvironment,TME)相互依存,微环境中各种分子和细胞均对肿瘤的发生发展及免疫治疗产生复杂的影响,其中TME的组成变化可能与免疫耐药有着密切关系。因此,本文阐述免疫耐药与肿瘤微环境的相关机制,旨在总结和寻找CRC免疫耐药的可能机制。

As the third malignant tumor in the world,colorectal cancer has caused a great burden on the society.In recent years,immunotherapy has been dominated by immune checkpoint inhibitors(ICIs).ICIs are highly effective in patients with microsatellite instability-high(MSI-H)or deficiency of mismatch repair(dMMR)metastatic colorectal cancer(mCRC),which provide new ways to treat advanced colorectal cancer.Although ICIs achieve significant therapeutic effects in mCRC patients with dMMR/MSI-H subtypes,only a few members of CRC patients can benefit from ICIs due to primary immune resistance.Besides,patients who benefit from initial ICIs may develop the secondary therapeutic resistance during the treatment process,which may ultimately lead to disease progression.However,tumor tissue is interdependent with the tumor microenvironment(TME),and various molecules and cells in the microenvironment have complex effects on the development of the tumor and immunotherapy.Among them,the composition change of TME may have a close relationship to immune resistance.Therefore,the mechanisms between immune resistance and the tumor microenvironment were elaborated to summarize and explore the possible mechanisms of immune resistance in colorectal cancer.