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

• Main Authors: Katharina Dötzer, Friederike Schlüter, Markus Bo Schoenberg, Alexandr V. Bazhin, Franz Edler von Koch, Andreas Schnelzer, Sabine Anthuber, Dieter Grab, Bastian Czogalla, Alexander Burges, Jens Werner, Sven Mahner, Barbara Mayer
• Format: Article
• Language: English
• Published: MDPI AG 2019-08-01
• Series: Cancers
• Subjects: ovarian cancer; metastatic lesions; tumor microenvironment; TILs; immune heterogeneity; platinum-sensitivity; immune checkpoints
• Online Access: https://www.mdpi.com/2072-6694/11/9/1250

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 (<i>n</i> = 23) and the peritoneum (<i>n</i> = 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 (<i>p</i> = 0.007), CD3 (<i>p</i> = 0.005), CD8 (<i>p</i> = 0.012), and PD-1 (programmed cell-death protein 1) (<i>p</i> = 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, <i>p</i> = 0.018; CD3, <i>p</i> = 0.037). Platinum-sensitive ovarian cancers revealed a higher intratumoral CD8⁺ infiltrate in the peritoneal lesions compared to the primary tumors (<i>p</i> = 0.045). In contrast, higher counts of stromal PD-1⁺ cells in the peritoneal lesions have been associated with reduced platinum-sensitivity (<i>p</i> = 0.045). Immune heterogeneity was associated with platinum response and might represent a selection marker for personalized therapy.