Dötzer Katharina, Schlüter Friederike, Schoenberg Markus Bo, Bazhin Alexandr V, von Koch Franz Edler, Schnelzer Andreas, Anthuber Sabine, Grab Dieter, Czogalla Bastian, Burges Alexander, Werner Jens, Mahner Sven, Mayer Barbara
Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Munich, Marchioninistraße 15, 81377 Munich, Germany.
German Cancer Consortium (DKTK), Partner Site Munich, Pettenkoferstraße 8a, 80336 Munich, Germany.
Cancers (Basel). 2019 Aug 26;11(9):1250. doi: 10.3390/cancers11091250.
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 ( = 23) and the peritoneum ( = 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 (=0.007), CD3 (=0.005), CD8 (=0.012), and PD-1 (programmed cell-death protein 1) (=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, =0.018; CD3, =0.037). Platinum-sensitive ovarian cancers revealed a higher intratumoral CD8 infiltrate in the peritoneal lesions compared to the primary tumors (=0.045). In contrast, higher counts of stromal PD-1 cells in the peritoneal lesions have been associated with reduced platinum-sensitivity (=0.045). Immune heterogeneity was associated with platinum response and might represent a selection marker for personalized therapy.
CD3和CD8淋巴细胞是原发性卵巢癌中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情况却知之甚少。在本研究中，对49例原发性肿瘤以及大网膜（n = 23）和腹膜（n = 15）中38个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敏感性相关联。对于所有免疫细胞表型，在配对的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性肿瘤，这在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）中得到体现。大网膜病变中CD45和CD3细胞的基质浸润较高与淋巴结转移的检测相关（CD45，P = 0.018；CD3，P = 0.037）。与原发性肿瘤相比，铂敏感的卵巢癌在腹膜病变中显示出更高的肿瘤内CD8浸润（P = 0.045）。相反，腹膜病变中基质PD-1细胞数量增加与铂敏感性降低相关（P = 0.045）。免疫异质性与铂反应相关，可能代表个性化治疗的选择标志物。
