Proteomics

Dataset Information

0

IgA transcytosis and tumor antigen recognition govern anti-tumor immunity in ovarian cancer


ABSTRACT: Although most ovarian cancers show prognostically relevant activated T-cell infiltrates, response rates to immune checkpoint inhibitors are very modest4. Memory B-cell and plasma cell infiltrates have been associated with better outcome in ovarian cancer, but the nature and functional relevance of these responses are controversial. Using 3 independent cohorts totaling 575 high-grade serous ovarian cancer (HGSOC) patients, we show that robust humoral responses are heavily dominated by the production of polyclonal IgA, which binds to Polymeric IgA Receptors universally expressed on ovarian cancer cells. Notably, all tertiary lymphoid structures identified in ~21% of HGSOCs contain IgA-producing oligoclonal B-cells. Strikingly, tumor Bcell-derived IgAs effectively target extracellular oncogenic drivers, whereas IgA transcytosis through malignant epithelial cells elicits transcriptional changes that antagonize the RAS pathway and that sensitize tumor cells to T-cell cytolytic killing, hindering malignant progression. Thus, tumor antigen-specific and antigen-independent IgA responses antagonize ovarian cancer growth by governing coordinated tumor cell, T-cell and B-cell responses. These findings provides a platform for the identification of novel targets spontaneously recognized by intratumoral B-cell-derived antibodies, and suggest that immunotherapies that augment B-cell responses may be more effective than T-cell-centric approaches, particularly for malignancies resistant to checkpoint inhibitors.

INSTRUMENT(S): Q Exactive HF, Q Exactive

ORGANISM(S): Homo Sapiens (human)

DISEASE(S): Malignant Neoplasm Of Ovary

SUBMITTER: John Koomen  

LAB HEAD: Jose Conejo-Garcia, MD/PhD

PROVIDER: PXD018079 | Pride | 2020-12-01

REPOSITORIES: Pride

altmetric image

Publications


Most ovarian cancers are infiltrated by prognostically relevant activated T cells<sup>1-3</sup>, yet exhibit low response rates to immune checkpoint inhibitors<sup>4</sup>. Memory B cell and plasma cell infiltrates have previously been associated with better outcomes in ovarian cancer<sup>5,6</sup>, but the nature and functional relevance of these responses are controversial. Here, using 3 independent cohorts that in total comprise 534 patients with high-grade serous ovarian cancer, we show that  ...[more]

Similar Datasets

2018-11-09 | PXD011228 | Pride
2022-03-08 | E-MTAB-11523 | biostudies-arrayexpress
2024-10-22 | PXD057019 | Pride
2021-12-20 | E-MTAB-10286 | biostudies-arrayexpress
2022-09-13 | PXD035757 | Pride
2023-11-01 | E-MTAB-12406 | biostudies-arrayexpress
2022-10-14 | PXD023923 | Pride
2022-10-14 | PXD023913 | Pride
2020-06-15 | PXD012811 | Pride
2020-07-03 | PXD020150 | Pride