Background: OC is a complex disease with diverse molecular driving mechanisms underneath histotype backgrounds. Intra-tumor heterogeneity (ITH), a mixture of distinct cell population, has yet to be elucidated in OC.
Method: DSP platform was adopted to investigate spatial clonal heterogeneity. Eighteen formalin-fixed paraffin embedded (FFPE) samples from the paired primary and metastatic sites of two Stage IV ovarian clear cell carcinoma (OCCC) and high-grade serous carcinoma (HGSC) patients were analyzed. 450 areas of interest (AOIs) were selected by pan-cytokeratin (PCK) and CD45 stains for epithelial and immune cell compartments. Tumor center (TC) and tumor periphery (TP) were annotated and compared by using a 28-plex immune-related protein panel for the differential expressions (log2FC > 1; p-value < 0.05) in the PCK and CD45 compartments.
Results: In the PCK compartment, OCCC showed higher expression of OX40L, and B7-H3 in the TC compared to HGSC. A similar trend of increased OX40L and B7-H3 expression was also observed in TP. Paradoxically, HGSC showed higher expression of STING and HLA-DR in the PCK compartments of TC and TP compared to OCCC. In the CD45 compartment, OCCC consistently showed higher expression of OX40L compared to HGSC in TC and TP. The increased expression of STING and HLA-DR in TC and TP of HGSC was also observed but with a less significant degree. A common feature between OCCC and HGSC was that CD68+ signals were more enriched in TC compared to TP in the CD45 compartment, suggestive of infiltrating macrophages.
Conclusion: OC showed distinct compositions of heterogeneity between TC and TP. CD68+ immune cells were more enriched in the TC. OCCC and HGSC showed paradoxical expression patterns of immune features indicative of antigen presenting cells (APC) in both tumor cells and microenvironments. Our data could provide evidence to guide the strategy for immunotherapy in OC.