Immune Heterogeneity Between Primary Tumors and Corresponding Metastatic Lesions and Response to Platinum Therapy in Primary Ovarian Cancer
Immune Heterogeneity Between Primary Tumors and Corresponding Metastatic Lesions and Response to Platinum Therapy in Primary Ovarian Cancer
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DOI：
10.3390/cancers11091250
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发表时间：
2019-09-01
期刊：
影响因子：
5.2
通讯作者：
Mayer, Barbara
中科院分区：
文献类型：
--
作者：
Doetzer, Katharina;Schlueter, Friederike;Mayer, Barbara
CD3(+)和CD8(+)淋巴细胞是原发性卵巢癌众所周知的预后标志物。相比之下，免疫浸润对治疗反应的预测价值以及原发性和转移性病变之间免疫异质性的参与却知之甚少。在本研究中，对 49 个原发性肿瘤和 38 个大网膜 (n = 23) 和腹膜 (n = 15) 相应病变的免疫浸润进行了免疫组织化学分析，并与临床病理因素和铂类敏感性相关。在所有免疫细胞表型的配对原发性和转移性病变之间观察到免疫异质性。大网膜病变中的基质免疫浸润高于原发肿瘤，这通过 CD45 (p = 0.007)、CD3 (p = 0.005)、CD8 (p = 0.012) 和 PD-1（程序性细胞死亡蛋白 1）（p = 0.013）反映出来。大网膜病变中CD45(+)和CD3(+)细胞间质浸润较高与淋巴结转移的检测相关(CD45, p = 0.018; CD3, p = 0.037)。与原发肿瘤相比，铂敏感卵巢癌的腹膜病变中肿瘤内 CD8(+) 浸润较高 (p = 0.045)。相反，腹膜病变中基质 PD-1(+) 细胞计数较高与铂敏感性降低相关 (p = 0.045)。免疫异质性与铂类反应相关，可能代表个性化治疗的选择标志。
CD3(+) and CD8(+) lymphocytes are well known prognostic markers in primary ovarian cancer. In contrast, the predictive value of the immune infiltrate concerning treatment response and the involvement of immune heterogeneity between primary and metastatic lesions are poorly understood. In this study, the immune infiltrate of 49 primary tumors and 38 corresponding lesions in the omentum (n = 23) and the peritoneum (n = 15) was immunohistochemically analyzed and correlated with clinicopathological factors and platinum-sensitivity. Immune heterogeneity was observed between paired primary and metastatic lesions for all immune cell phenotypes. The stromal immune infiltrate was higher in the omental lesions than in the primary tumors, which was reflected by CD45 (p = 0.007), CD3 (p = 0.005), CD8 (p = 0.012), and PD-1 (programmed cell-death protein 1) (p = 0.013). A higher stromal infiltrate of both CD45(+) and CD3(+) cells in the omental lesions was associated with the detection of lymph node metastasis (CD45, p = 0.018; CD3, p = 0.037). Platinum-sensitive ovarian cancers revealed a higher intratumoral CD8(+) infiltrate in the peritoneal lesions compared to the primary tumors (p = 0.045). In contrast, higher counts of stromal PD-1(+) cells in the peritoneal lesions have been associated with reduced platinum-sensitivity (p = 0.045). Immune heterogeneity was associated with platinum response and might represent a selection marker for personalized therapy.