Comparison of immunological characteristics between paired mismatch repair-proficient and -deficient colorectal cancer patients.
Comparison of immunological characteristics between paired mismatch repair-proficient and -deficient colorectal cancer patients.
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配对错配修复良好和缺陷的结直肠癌患者免疫学特征的比较
DOI：
10.1186/s12967-018-1570-z
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发表时间：
2018-07-13
影响因子：
7.4
通讯作者：
Xia LP
中科院分区：
文献类型：
--
作者：
Liu SS;Yang YZ;Jiang C;Quan Q;Xie QK;Wang XP;He WZ;Rong YM;Chen P;Yang Q;Yang L;Zhang B;Xia XJ;Kong PF;Xia LP
背景：目前，错配修复缺陷（dMMR）状态是大肠癌（CRC）患者靶向免疫检查点抑制治疗的一个有希望的候选者，然而，潜在的免疫学机制尚未很好地阐明，其他一些预测因素也需要挖掘。方法：通过配对失配修复熟练（167）和dMMR(163)，收集330例结直肠癌患者，探讨MMR状态与MHC I类、CD3、CD4、CD8、CD56、程序性死亡-1、程序性死亡配体-1等重要免疫分子的关系，探讨dMMR状态和MHC I类低表达的危险因素。采用Pearson卡方检验分析临床病理和免疫特征与MMR状态的相关性，采用两类logistic回归模型进行单因素和多因素分析，预测dMMR状态和MHC I类低表达的危险因素的比值比。结果：多因素logistic回归分析显示，MHC I类、CD4低表达、CD8高表达是dMMR状态的显著危险因素[比值比（OR）分别为24.66、2.94、2.97；dMMR状态是MHC I类低表达的唯一危险因素（OR = 15.34; p < 0.001）。结论：高CD8和低MHC I类表达提示dMMR CRC患者免疫微环境的矛盾性和复杂性。其他一些免疫细胞如CD56+细胞也可能参与免疫检查点抑制的过程，这需要进一步的研究。
Background:Currently, mismatch repair-deficient (dMMR) status is a promising candidate for targeted immune checkpoint inhibition therapy in colorectal cancer (CRC) patients, however, the potential immunological mechanism has not yet been well clarified and some other predictors need to be excavated as well.Methods:We collected 330 CRC patients by the match of mismatch repair-proficient (167) and dMMR (163), explored the relationship between MMR status and some important immune molecules including MHC class I, CD3, CD4, CD8, CD56, programmed death-1 and programmed death ligand-1, and investigated the risk factors for dMMR status as well as low MHC class I expression. The Pearson Chi square test was used for analyzing the associations between clinicopathological and immune characteristics and MMR status, and two categories logistic regression model was used for univariate and multivariate analysis to predict the odds ratio of risk factors for dMMR status and low MHC class I expression.Results:Multivariate logistic regression analysis showed that low MHC class I and CD4 expression and high CD8 expression were significant risk factors for dMMR status [odds ratio (OR) = 24.66, 2.94 and 2.97, respectively; all p < 0.05] and dMMR status was the only risk factor for low MHC class I expression (OR = 15.34; p < 0.001).Conclusions:High CD8 and low MHC class I expression suggests the contradiction and complexity of immune microenvironment in dMMR CRC patients. Some other immunocytes such as CD56+cells might also participate in the process of immune checkpoint inhibition, whereas needs further investigations.
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影响因子：
158.5
作者：
Hampel, H;Frankel, WL;Papadopoulos, N
通讯作者：
Papadopoulos, N
影响因子：
24.5
作者：
Simpson, Jonathan A. D.;Al-Attar, Ahmad;Durrant, Lindy G.
通讯作者：
Durrant, Lindy G.
DOI：
10.1158/1078-0432.ccr-15-0715
发表时间：
2016-01-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Sabbatino F;Villani V;Yearley JH;Deshpande V;Cai L;Konstantinidis IT;Moon C;Nota S;Wang Y;Al-Sukaini A;Zhu AX;Goyal L;Ting DT;Bardeesy N;Hong TS;Fernandez-del Castillo C;Tanabe KK;Lillemoe KD;Ferrone S;Ferrone CR
通讯作者：
Ferrone CR
影响因子：
28.2
作者：
Llosa, Nicolas J.;Cruise, Michael;Housseau, Franck
通讯作者：
Housseau, Franck
影响因子：
7.3
作者：
Paul S;Lal G
通讯作者：
Lal G