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Open AccessArticle

Immune Heterogeneity Between Primary Tumors and Corresponding Metastatic Lesions and Response to Platinum Therapy in Primary Ovarian Cancer

1
Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Munich, Marchioninistraße 15, 81377 Munich, Germany
2
German Cancer Consortium (DKTK), Partner Site Munich, Pettenkoferstraße 8a, 80336 Munich, Germany
3
Department of Obstetrics and Gynecology, Klinikum Dritter Orden, Menzinger Straße 44, 80638 Munich, Germany
4
Department of Obstetrics and Gynecology, Klinikum rechts der Isar, Technical University Munich, Ismaninger Straße 22, 81675 Munich, Germany
5
Department of Obstetrics and Gynecology, Clinic Starnberg, Oßwaldstraße 1, 82319 Starnberg, Germany
6
Department of Obstetrics and Gynecology, Clinic Harlaching, Sanatoriumsplatz 2, 81545 Munich, Germany
7
Department of Obstetrics and Gynecology, University Hospital, Ludwig-Maximilians-University Munich, Marchioninistraße 15, 81377 Munich, Germany
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(9), 1250; https://doi.org/10.3390/cancers11091250
Received: 4 August 2019 / Accepted: 14 August 2019 / Published: 26 August 2019
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. View Full-Text
Keywords: ovarian cancer; metastatic lesions; tumor microenvironment; TILs; immune heterogeneity; platinum-sensitivity; immune checkpoints ovarian cancer; metastatic lesions; tumor microenvironment; TILs; immune heterogeneity; platinum-sensitivity; immune checkpoints
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MDPI and ACS Style

Dötzer, K.; Schlüter, F.; Schoenberg, M.B.; Bazhin, A.V.; Edler von Koch, F.; Schnelzer, A.; Anthuber, S.; Grab, D.; Czogalla, B.; Burges, A.; Werner, J.; Mahner, S.; Mayer, B. Immune Heterogeneity Between Primary Tumors and Corresponding Metastatic Lesions and Response to Platinum Therapy in Primary Ovarian Cancer. Cancers 2019, 11, 1250. https://doi.org/10.3390/cancers11091250

AMA Style

Dötzer K, Schlüter F, Schoenberg MB, Bazhin AV, Edler von Koch F, Schnelzer A, Anthuber S, Grab D, Czogalla B, Burges A, Werner J, Mahner S, Mayer B. Immune Heterogeneity Between Primary Tumors and Corresponding Metastatic Lesions and Response to Platinum Therapy in Primary Ovarian Cancer. Cancers. 2019; 11(9):1250. https://doi.org/10.3390/cancers11091250

Chicago/Turabian Style

Dötzer, Katharina; Schlüter, Friederike; Schoenberg, Markus B.; Bazhin, Alexandr V.; Edler von Koch, Franz; Schnelzer, Andreas; Anthuber, Sabine; Grab, Dieter; Czogalla, Bastian; Burges, Alexander; Werner, Jens; Mahner, Sven; Mayer, Barbara. 2019. "Immune Heterogeneity Between Primary Tumors and Corresponding Metastatic Lesions and Response to Platinum Therapy in Primary Ovarian Cancer" Cancers 11, no. 9: 1250. https://doi.org/10.3390/cancers11091250

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