Tumor and local lymphoid tissue interaction determines prognosis in high-grade serous ovarian cancer

Haonan Lu; Hantao Lou; Georg Wengert; Reema Paudel; Naina Patel; Saral Desai; Bill Crum; Kristofer Linton-Reid; Mitchell Chen; Dongyang Li; Jacey Ip; Francesco Mauri; David J Pinato; Andrea Rockall; Susan J Copley; Sadaf Ghaem-Maghami; Eric O Aboagye

doi:10.1016/j.xcrm.2023.101092

Tumor and local lymphoid tissue interaction determines prognosis in high-grade serous ovarian cancer

Cell Rep Med. 2023 Jul 18;4(7):101092. doi: 10.1016/j.xcrm.2023.101092. Epub 2023 Jun 21.

Authors

Haonan Lu¹, Hantao Lou², Georg Wengert¹, Reema Paudel¹, Naina Patel¹, Saral Desai³, Bill Crum¹, Kristofer Linton-Reid¹, Mitchell Chen⁴, Dongyang Li¹, Jacey Ip⁴, Francesco Mauri¹, David J Pinato⁵, Andrea Rockall¹, Susan J Copley⁴, Sadaf Ghaem-Maghami⁴, Eric O Aboagye⁶

Affiliations

¹ Department of Surgery and Cancer, Imperial College, Hammersmith Campus, The Commonwealth Building, Du Cane Road, W12 0NN London, UK.
² Ludwig Cancer Research, Nuffield Department of Medicine, University of Oxford, OX3 7DQ Oxford, UK.
³ Imperial College Healthcare NHS Trust, Du Cane Road, W12 0HS London, UK.
⁴ Department of Surgery and Cancer, Imperial College, Hammersmith Campus, The Commonwealth Building, Du Cane Road, W12 0NN London, UK; Imperial College Healthcare NHS Trust, Du Cane Road, W12 0HS London, UK.
⁵ Department of Surgery and Cancer, Imperial College, Hammersmith Campus, The Commonwealth Building, Du Cane Road, W12 0NN London, UK; Division of Oncology, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy.
⁶ Department of Surgery and Cancer, Imperial College, Hammersmith Campus, The Commonwealth Building, Du Cane Road, W12 0NN London, UK. Electronic address: eric.aboagye@imperial.ac.uk.

Abstract

Tertiary lymphoid structure (TLS) is associated with prognosis in copy-number-driven tumors, including high-grade serous ovarian cancer (HGSOC), although the function of TLS and its interaction with copy-number alterations in HGSOC are not fully understood. In the current study, we confirm that TLS-high HGSOC patients show significantly better progression-free survival (PFS). We show that the presence of TLS in HGSOC tumors is associated with B cell maturation and cytotoxic tumor-specific T cell activation and proliferation. In addition, the copy-number loss of IL15 and CXCL10 may limit TLS formation in HGSOC; a list of genes that may dysregulate TLS function is also proposed. Last, a radiomics-based signature is developed to predict the presence of TLS, which independently predicts PFS in both HGSOC patients and immune checkpoint inhibitor (ICI)-treated non-small cell lung cancer (NSCLC) patients. Overall, we reveal that TLS coordinates intratumoral B cell and T cell response to HGSOC tumor, while the cancer genome evolves to counteract TLS formation and function.

Keywords: CNA; ovarian cancer; radiomics; tertiary lymphoid structures.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Non-Small-Cell Lung*
Cystadenocarcinoma, Serous*
Female
Humans
Lung Neoplasms* / pathology
Lymphoid Tissue
Ovarian Neoplasms* / pathology
Prognosis

Grants and funding

WT_/Wellcome Trust/United Kingdom