國家衛生研究院 NHRI:Item 3990099045/15587
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    题名: The prognostic role of LAG-3 expression in metastatic colorectal cancer
    作者: Huang, YH;Lee, CT;Lin, PC;Chan, RH;Chen, PC;Lin, BW;Shen, MR;Chen, SH;Yeh, YM
    贡献者: National Institute of Cancer Research
    摘要: Background: Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint receptor that negatively regulates T cell activation and inhibits the immune microenvironment. We explored the prognostic effect of LAG-3-positive tumor-infiltrating lymphocytes (TILs) in metastasis colorectal cancer (mCRC) and its correlation with important genomic alterations of mCRC. Methods: A total of 139 patients with mCRC were enrolled. Tissues from both the primary tumor and distant metastasis were evaluated for LAG-3 expression by immunohistochemical (IHC) staining. LAG-3 staining of TILs in either the tumor front or tumor center were considered positive. The level of LAG-3 expression was reported as the number of LAG-3-positive immune cells in one high-power field (HPF). Results: LAG-3 expression was evaluated in 116 primary and 98 metastatic tumor samples. The level of LAG3 expression was higher in the primary tumors compared to the metastatic tumors (median 1.35 vs. 0.55/HPF, p ¼ 0.033). We analyzed the clinicopathologic feature in populations with different levels of LAG3 expression (LAG3+ TIL >0 vs. ¼0/HPF; 1 vs. <1; 3 vs. <3; 5 vs. <5; 10 vs. <10) in primary and metastatic tumor, respectively. In patients with primary tumors of LAG-3+ TIL >0, there was higher percentage of RAS mutation [54% vs. 20%, p¼ 0.007]. Patients with primary tumors of LAG-3+ TIL 5 more frequently exhibited high tumor mutation burden (TMB 10 mutations/mb) tumor than those of LAG-3+ TIL <5 [18% vs. 3%, p¼ 0.0036]. In subgroups of primary tumors with LAG-3 expression of 3, 5 and 10 or greater, overall survival (OS) were shorter than those with LAG-3 expression less than 3, 5 and 10, respectively [median: LAG-3+ TIL 3 vs. <3, 30.1 vs. 45.2 months, Hazard ratio (HR) 1.687, p ¼ 0.035; 5 vs. <5, 28.3 vs. 44.6 months, HR 1.791, p ¼ 0.025; 10 vs. <10, 28.0 vs. 45.2 months, HR 2.137, p ¼ 0.0073]. This difference was not observed in metastatic tumors. Notably, in metastatic tumors, OS was longer in the LAG-3 >0 than LAG-3¼0 group (51.9 vs. 32.5 months, HR 0.513, p ¼ 0.0208). Conclusions: LAG-3 expression level in primary CRC tumor was associated with negative survival outcome and can serve as a potential prognostic marker. Further studies are needed to explore the optimal cutoff level to identify the candidates that benefit most from LAG-3 blockade.
    日期: 2023-11
    關聯: Annals of Oncology. 2023 Nov;34(Suppl. 4):S1514-S1515.
    Link to: http://dx.doi.org/10.1016/j.annonc.2023.10.249
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0923-7534&DestApp=IC2JCR
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