Shicheng Su’s Group Discovered the Opposite Effects of B Cells in Tumor Regulated by Complement Signals
In March 5th, Research Prof. Shicheng Su’s group published a cancer immunotherapy related article in Cell. The research discovered the mechanism of the opposite effects of tumor-infiltrating B cells, which are regulated by complement. The results of this article provide promising markers for neoadjuvant chemotherapy induced anti-tumor immunity and help anticipating the therapeutic efficacy for patients. Comments recommending this research have been published in journals including Cell, Nature Immunology Review and Cancer Discovery.
The rapid development of cancer immunotherapy has brought new hope to cancer patients. B cell, which is an important part of immune microenvironment, is reported to play a conflicting role in anti-tumor immunity. B cells were reported to promote tumor progression in previous studies, while clinical research published recently showed that tumors with more infiltrated B cells respond better in immunotherapy. It indicates that the tumor-associated B cells have phenotypic and functional heterogeneity, and B cells are likely to be the key in determining the effect of immunotherapy.
The researchers isolated B cells from breast cancer tissues of patients before and after receiving neo-adjuvant chemotherapy, and discovered a subset of B cells characterized by ICOSL+CR2highIL-10-CD20+CD38+CD27+IgA-IgD- emerging after chemotherapy by single-cell sequencing. Using an Automated Image Analysis with Background Subtraction (AIABS) system, the research demonstrated the location of this subset of B cells, which is mainly in the tertiary lymphoid organs formed after chemotherapy. Furthermore, employing the B-cell-specific ICOSL/CR2 knockout mice, they found that ICOSL+ B cells promote anti-tumor immunity by activating T cells through ICOSL-ICOS pathway and the complement activation triggered by immunogenic tumor cell death induces the generation of ICOSL+ B cells. The study proposed that the complement inhibitory protein expressed by tumor cells determines the conflicting roles of B cells in various types of cancer. B cells with anti-tumor phenotype and the related regulatory molecules are potential targets for breast cancer immunotherapy.
Dr. Yiwen Lu, Associate Research Professor Qiyi Zhao, and Associate Research Professor Jian-You Liao are co-first authors. Academician Erwei Song provided valuable advice and strong support for this project.
Hyperlink of the article: https://doi.org/10.1016/j.cell.2020.02.015