Department of Gynecologic Oncology, and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Statistics, George R. Brown School of Engineering, Rice University, Houston, Texas.
Clin Cancer Res. 2017 Aug 1;23(15):4473-4481. doi: 10.1158/1078-0432.CCR-16-2655. Epub 2017 Mar 6.
Recent studies show that colorectal tumors with high microsatellite instability (MSI-H) have increased immunogenicity and response to immunotherapy compared with microsatellite-stable (MSS) tumors. It is not yet clear whether MSI-H endometrial cancer may also benefit from these therapies. It is also unknown whether immune response is equivalent in MSI-H endometrial cancer with sporadic or inherited Lynch syndrome origins. Multiplexed fluorescent IHC was used to compare matched MSI-H ( = 60) and MSS ( = 96) endometrial cancer specimens by evaluating immune cell populations in tumor and stroma compartments. Sporadic MSI-H and Lynch syndrome-associated (LS) MSI-H endometrial cancers were also directly compared. Increased immune cells were present in stroma of MSI-H endometrial cancer compared with MSS, including granzyme B cells, activated CTLs (CD8granzyme B), and PD-L1 cells. Granzyme B cells and activated CTLs were also increased in the tumor compartment of MSI-H endometrial cancers. Comparing sporadic and LS MSI-H endometrial cancer showed distinct differences in immune cell populations, indicating that mechanisms underlying microsatellite instability alter immune response. Specifically, LS MSI-H endometrial cancer showed increased CD8 cells and activated CTLs in stroma, with reduced macrophages in stroma and tumor compared with sporadic MSI-H. Sporadic MSI-H had increased PD-L1 macrophages in stroma and tumor compared with LS MSI-H endometrial cancer. MSI-H endometrial cancer has increased immune cell infiltration compared with MSS endometrial cancer and the hereditary or sporadic origin of microsatellite instability impacts immune response. Clinical trials to determine the role of immunotherapy in patients with MSI-H endometrial cancer must evaluate Lynch syndrome-related and sporadic MSI-H tumors separately. .
最近的研究表明，与微卫星稳定（MSS）肿瘤相比，具有高微卫星不稳定性（MSI-H）的结直肠肿瘤具有更高的免疫原性和对免疫治疗的反应。目前尚不清楚 MSI-H 子宫内膜癌是否也可能受益于这些治疗方法。也不清楚免疫反应是否在散发性或遗传性林奇综合征起源的 MSI-H 子宫内膜癌中是等效的。通过评估肿瘤和基质区室中免疫细胞群体，使用多重荧光免疫组化比较匹配的 MSI-H（n=60）和 MSS（n=96）子宫内膜癌标本。还直接比较了散发性 MSI-H 和林奇综合征相关（LS）MSI-H 子宫内膜癌。与 MSS 相比，MSI-H 子宫内膜癌的基质中存在更多的免疫细胞，包括颗粒酶 B 细胞、活化的 CTL（CD8+颗粒酶 B）和 PD-L1 细胞。MSI-H 子宫内膜癌的肿瘤区室中也增加了颗粒酶 B 细胞和活化的 CTL。比较散发性和 LS MSI-H 子宫内膜癌显示出免疫细胞群体的明显差异，表明微卫星不稳定性的机制改变了免疫反应。具体而言，LS MSI-H 子宫内膜癌在基质中显示出更多的 CD8 细胞和活化的 CTL，与散发性 MSI-H 相比，基质和肿瘤中的巨噬细胞减少。与 LS MSI-H 子宫内膜癌相比，散发性 MSI-H 子宫内膜癌的基质和肿瘤中 PD-L1 巨噬细胞增加。与 MSS 子宫内膜癌相比，MSI-H 子宫内膜癌有更多的免疫细胞浸润，并且微卫星不稳定性的遗传或散发性起源会影响免疫反应。在评估 MSI-H 子宫内膜癌患者免疫治疗作用的临床试验中，必须分别评估林奇综合征相关和散发性 MSI-H 肿瘤。
