Nielsen Amalie Thomsen, Saqi Ida Kolukisa, Justesen Tobias Freyberg, Madsen Michael Tvilling, Gögenur Ismail, Orhan Adile
Center for Surgical Science, Department of Surgery, Zealand University Hospital, Køge, Denmark.
Center for Surgical Science, Department of Surgery, Zealand University Hospital, Køge, Denmark.
Crit Rev Oncol Hematol. 2025 Jul;211:104714. doi: 10.1016/j.critrevonc.2025.104714. Epub 2025 Apr 4.
Tumor mutations and the composition of the tumor microenvironment have prognostic and therapeutic significance in colorectal cancer (CRC). However, immunotherapy remains a challenge for patients with proficient mismatch repair (pMMR) CRC. In this paper, the association between tumor-infiltrating lymphocytes (TILs) and tumor mutations on survival outcomes in patients with localized pMMR CRC was examined.
A systematic review of the literature and a meta-analysis were conducted in accordance with the PRISMA guidelines. The literature search was conducted in PubMed, Embase, Cochrane Library, and Web of Science. The outcomes of interest were overall survival, disease-free survival, and cancer-specific survival. The risk of bias was assessed through the Newcastle-Ottawa Scale and the quality of the cumulative evidence was evaluated through the modified GRADE approach.
In total, 8498 articles were screened for eligibility and 44 articles were included in the meta-analysis with 33,704 patients in total. Patients with high infiltration of any TILs showed significantly improved overall survival (HR = 0.57, 95 % CI: 0.49-0.67, I: 0 %), especially for the subgroup of CD3 + (HR = 0.52, 95 % CI: 0.38-0.71, I: 0 %) and CD8 + (HR = 0.60, 95 % CI: 0.37-0.99, I: 10 %) TILs. Patients with BRAF mutation (HR = 2.68, 95 % CI: 1.47-4.89, I: 83 %) and KRAS mutation (HR = 1.25, 95 % CI: 1.18-1.33, I: 0 %) showed decreased overall survival.
High infiltration of TILs, especially CD3 + and CD8 + , was associated with significantly improved survival, while BRAF and KRAS mutations were correlated with worse survival outcomes for patients with non-metastatic pMMR CRC.
肿瘤突变和肿瘤微环境的组成在结直肠癌（CRC）中具有预后和治疗意义。然而，免疫治疗对错配修复功能正常（pMMR）的CRC患者仍然是一项挑战。本文研究了局限性pMMR CRC患者中肿瘤浸润淋巴细胞（TILs）与肿瘤突变对生存结局的关联。
按照PRISMA指南进行文献系统综述和荟萃分析。在PubMed、Embase、Cochrane图书馆和Web of Science中进行文献检索。感兴趣的结局为总生存期、无病生存期和癌症特异性生存期。通过纽卡斯尔-渥太华量表评估偏倚风险，并通过改良的GRADE方法评估累积证据的质量。
共筛选出8498篇文章以确定其 eligibility，44篇文章纳入荟萃分析，共33704例患者。任何TILs高浸润的患者总生存期显著改善（HR = 0.57，95%CI：0.49 - 0.67，I：0%），尤其是CD3 +（HR = 0.52，95%CI：0.38 - 0.71，I：0%）和CD8 +（HR = 0.60，95%CI：0.37 - 0.99，I：10%）TILs亚组。BRAF突变（HR = 2.68，95%CI：1.47 - 4.89，I：83%）和KRAS突变（HR = 1.25，95%CI：1.18 - 1.33，I：0%）的患者总生存期降低。
TILs高浸润，尤其是CD3 +和CD8 +，与生存显著改善相关，而BRAF和KRAS突变与非转移性pMMR CRC患者较差的生存结局相关。
