Enhanced Efficacy of Simultaneous PD-1 and PD-L1 Immune Checkpoint Blockade in High-Grade Serous Ovarian Cancer

Abstract

Competing interests: M.B. receives sponsored research support from Novartis. M.B. serves as a consultant and scientific advisor to Kronos Bio, H3 Biomedicine and GV20 Therapeutics. In the past M.B. served as a scientific advisor to GTx, Inc. and as consultant to Aleta BioTherapeutics. U.A.M. is a consultant for Novartis and Merck, is on the scientific advisory boards for 2X Oncology and the Clearity Foundation, and is an uncompensated advisor for AstraZeneca. X.S.L. is a cofounder and board member of GV20 Oncotherapy, on the scientific advisory board of 3DMed Care, a consultant for Genentech, and a stock holder of BMY, TMO, WBA, ABT, ABBV, and JNJ. S.J.H. receives sponsored research support from Eli Lilly and Company and AstraZeneca. B.R. is an uncompensated scientific advisory board member for VincenTech. B.R. receives sponsored research support from Palleon Pharmaceuticals and Mercy Bioanalytics. Neither is directly related to the proposed research.

Organoids of the Female Reproductive Tract: Innovative Tools to Study Desired to Unwelcome Processes

“…The prospect of more complex organoid models also encompassing immune, stromal and/or vascular cells, raises the hope to in the future test clinically relevant drugs that tackle neo-angiogenesis and tumor immunology. Indeed, shortterm 3D spheroid co-cultures of HGSOC cells with immune cells have shown sensitivity to immune checkpoint inhibitors (Wan et al, 2020).…”

Recent Advances in Integrative Multi-Omics Research in Breast and Ovarian Cancer

“…Moreover, scRNA-seq has been used to develop gene-expression-signature of the myeloid-derived suppressor cells (MDSCs) in addition to identifying CD84 as a surface biomarker for MDSCs in breast cancer [ 202 ]. Similarly, Wan et al reported reprogramming of inert natural killer and T cells to a highly active cytotoxic state following bispecific anti-PD-1orPD-L1 antibody treatment using single-cell RNA-seq analysis of HGSOC organoid co-cultures; this study identified a potential advantage of bispecific antibodies in immune checkpoint blockade therapy in HGSOC [ 203 ]. Further analyses have identified inter- and intra-tumor heterogeneity in cancer associated fibroblasts cell states in HGSOC and breast cancer [ 117 , 204 ].…”

Patient-derived organoids and high grade serous ovarian cancer: from disease modeling to personalized medicine

“…Nevertheless, one limitation of PDOs is currently represented by the lack of reliable protocols capable to faithfully reproduce the tumor microenvironment, which comprises the stroma, immune cells and blood vessels [6,[8][9][10][67][68][69][70][71][72][73][74]. However, the recent development of organoids cocultured with tumor microenvironment components holds promise for the possibility to evaluate complex features of tumors in the near future [76,77]. Short term PDO cultures were recently shown to maintain tumor infiltrating immune cells and have been successfully employed for comparative analyses of immune checkpoint therapies responses [77].…”

“…However, the recent development of organoids cocultured with tumor microenvironment components holds promise for the possibility to evaluate complex features of tumors in the near future [76,77]. Short term PDO cultures were recently shown to maintain tumor infiltrating immune cells and have been successfully employed for comparative analyses of immune checkpoint therapies responses [77]. Moreover, in cancers characterized by a high tumor mutational burden, coculture of PDOs with peripheral blood lymphocytes generated CD8+ T cell clones specifically reactive against neoplastic cells, thus potentially valuable for adoptive cell transplantation [78].…”