Source: Sun Yat-Sen Memorial Hospital
Written by: Sun Yat-Sen Memorial Hospital
Edited by: Tan Rongyu, Wang Dongmei

On March 5th, Research Prof. Shicheng Su’s group from Sun Yat-Sen Memorial Hospital of Sun Yat-sen University published a cancer immunotherapy related article in Cell. The research discovered the mechanism of the conflicting effects of tumor-infiltrating B cells regulated by complement. The results of this article provide promising markers for chemotherapy induced anti-tumor immunity and help anticipating the effectiveness of chemotherapy for patients. Comments recommended this research achievement have been published in journals including Cell, Nature Immunology Review and Cancer Discovery. Dr. Yiwen Lu, Associate Research Professor Qiyi Zhao, and Associate Research Professor Jian-You Liao from Sun Yat-sen University are co-first authors. Academician Erwei Song provided valuable advice and strong support for this project.

In recent years, the rapid development of cancer immunotherapy has brought new hope to cancer patients. As an important part of immune microenvironment, B cell is reported to play a conflicting role in anti-tumor immunity. Previous studies found that B cells could promote tumor progression, while clinical research published recently showed that tumors with more infiltrated B cells respond better in immunotherapy. It suggests 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 found a subset of B cells characterized by ICOSL⁺CR2^highIL-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 revealed 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 discovered 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.

Link to the paper: https://doi.org/10.1016/j.cell.2020.02.015