The function that B cells play in the fight against cancer has been the subject of more in-depth immunology research carried out under the direction of Harvard Medical School. The team identifies a crucial checkpoint of B-cell activation and how bypassing the checkpoint could unlock T-cell potential in a paper that was published in Nature and is titled “B-cell-specific checkpoint molecules that regulate anti-tumor immunity.”
Various B-cell types were studied during melanoma growth, and gene expression levels were tracked with high-throughput flow cytometry, bulk, and single-cell RNA sequencing.
They discovered that melanoma tumor growth was significantly accelerated worldwide when B-cells were destroyed.
A subset of B-cells that explicitly grows in the depleting lymph hub in cancer-bearing mice was distinguished. The Havcr1 gene is responsible for the expression of the cell surface molecule TIM-1 by this expanding B-cell subset. Co-inhibitory molecules like PD-1, TIM-3, TIGIT, and LAG-3 are also present in the subset.
On B-cells, conditional deletion of the co-inhibitory molecules had little to no effect on the amount of tumor that was present. However, tumor growth was significantly slowed down in B cells when Havcr1 was selectively deleted.
In knockout mice, the absence of TIM-1 and the consequent increase in B-cell activation and antigen presentation resulted in an increase in the activity of tumor-specific T cells.
The administration of a high-affinity anti-TIM-1 antibody, which is available on the market, also stopped the growth of the tumor. There was no effect when the Havcr1 gene was removed from T-cells, indicating that the effect was B-cell dependent.
In comparison to T cells, specific B-cell tumor-related mechanisms are poorly understood. All the more, for the most part, it is a cooperative exertion through a fountain of intracellular motion toward mounting a compelling resistant reaction against microorganisms. There are signals in this system that both start and stop the immune response.
The expression of TIM-1 by this particular B-cell subset may act as a healthy regulatory check on T-cell activation, suppressing an excessive immune response. It’s possible that this healthy function has nothing to do with tumor growth, which would put it at odds with the immune system’s ability to attack tumor cells more aggressively.
By fostering intratumoral B-cell and T-cell cooperation, B-cell responses have previously been linked to positive outcomes in multiple cancers. According to the findings of this study, TIM-1 may inhibit B-cell activation, antigen presentation, and T-cell activation in a causal manner.
The immune system may be able to mobilize anti-tumor immunity and prevent tumor growth by manipulating or suppressing B-cells that express TIM-1.
More information: Lloyd Bod et al, B-cell-specific checkpoint molecules that regulate anti-tumour immunity, Nature (2023). DOI: 10.1038/s41586-023-06231-0
Uncovering a role for B cells in antitumour immunity, Nature (2023). DOI: 10.1038/d41586-023-01678-7
