Aruquipa Marcelo Porfirio Sunagua, Donadio Mauro S, Peixoto Renata D
Gastrointestinal Oncology Department, Oncoclinicas, São Paulo 04513-100, Brazil.
https://orcid.org/0009-0009-0207-0022.
Ecancermedicalscience. 2024 Sep 18;18:1771. doi: 10.3332/ecancer.2024.1771. eCollection 2024.
Microsatellite stable (MSS) metastatic colorectal cancer (CRC) remains predominantly managed with chemotherapy. The use of immunotherapy, whether alone or in combination with other systemic or local treatments, displays limited success, especially in the context of active liver metastases (LM). The mechanisms responsible for this resistance are not fully understood.
We conducted a comprehensive search across electronic databases such as Medline, PubMed, Google Scholar and ScienceDirect. This search targeted translational studies evaluating the liver tumour immune microenvironment and immune tolerance mechanisms in CRC with LM and prospective studies that assessed immunotherapy either as a standalone treatment or in combination with other systemic or local therapies for patients diagnosed with MSS CRC. Our primary objectives included elucidating the mechanisms of resistance originating from LM in a non-systematic literature review and presenting a summary of the outcomes observed in prospective trials utilising immune checkpoint inhibitors (ICIs), with a focus on the presence of LM.
There were 16 prospective trials evaluating immunotherapy for metastatic CRC comprising 1,713 patients. Response rates to immunotherapy inpatients with colorectal liver metastases (CRLM) varied from 0% to 23%. Overall, reduced or null responses to immunotherapy in the presence of liver metastasis in comparison to patients without liver involvement were observed.
Studies consistently show the resistance derived from classical ICI, both alone and in combination with other systemic treatments in patients with CRLM. The design of upcoming trials using immunotherapy should consider LM as a stratification factor or contemplate excluding patients with liver involvement.
微卫星稳定（MSS）的转移性结直肠癌（CRC）仍主要采用化疗进行治疗。免疫疗法无论是单独使用还是与其他全身或局部治疗联合使用，其成功率都有限，尤其是在存在活动性肝转移（LM）的情况下。导致这种耐药性的机制尚未完全明确。
我们在电子数据库（如Medline、PubMed、谷歌学术和ScienceDirect）中进行了全面检索。该检索针对评估伴有LM的CRC患者肝脏肿瘤免疫微环境和免疫耐受机制的转化研究，以及评估免疫疗法作为单一治疗或与其他全身或局部疗法联合用于诊断为MSS CRC患者的前瞻性研究。我们的主要目标包括在非系统性文献综述中阐明源于LM的耐药机制，并总结在前瞻性试验中使用免疫检查点抑制剂（ICI）观察到的结果，重点关注LM的存在情况。
有16项评估转移性CRC免疫疗法的前瞻性试验，共纳入1713例患者。结直肠肝转移（CRLM）患者对免疫疗法的反应率在0%至23%之间。总体而言，与无肝转移的患者相比，存在肝转移的患者对免疫疗法的反应降低或无反应。
研究一致表明，经典ICI无论是单独使用还是与其他全身治疗联合使用，在CRLM患者中均存在耐药性。未来使用免疫疗法的试验设计应将LM作为分层因素，或考虑排除有肝转移的患者。
