A new study in mice finds that B cells unexpectedly promote the therapeutic shrinking of breast cancer tumours, even when they are not the direct targets of local immunotherapy.
The new study, published in Science Immunology, could one day be used to boost cancer immunotherapy when treating hard-to-reach tumours.
The abscopal effect
Frequently, patients with cancer have more than one tumour, some of which may be in places that are harder to treat with immunotherapy. In these instances, oncologists usually treat the easier-to-access tumour and look for abscopal effects on more remote ones.
The abscopal effect describes the shrinking of tumours in parts of the body that were not the direct target of local therapy. Although the exact biological mechanisms responsible for the abscopal effect are still being studied, the immune system is believed to play an important role. One school of thought is that in response to radiation, tumour cells may release material that is recognised by the immune system as a threat. This potentially leads to an immune response throughout the body.
Many researchers have long been experimenting with combinations of treatments hoping to improve the chances that the abscopal effect will occur in patients with metastatic cancer.
Surprising B cells
Researchers at Stanford University used a 2-tumour mouse model to study the pathways that lead to abscopal responses during cancer immunotherapy.
One tumour was injected with an innate immune toll-like receptor called CpG and a protein known as IL-12Fc. Both CpG and IL-12Fc are associated with positive outcomes in cancer therapy. The team found that both tumours regressed as a result.
Antitumor T cell responses are the main mediators of cancer immunotherapy. However, many other features of the immune system are needed for efficient T cell responses to be generated.
Unexpectedly, the researchers found that B cells were activated by the treatment and were required for optimal T cell activation. The abscopal response came from T cells and B cells in combination.
“[It’s] a surprising and useful discovery, since less is known about B cells in the context of cancer therapeutics,” the authors noted.
Boosting antitumour approaches
Next, the team looked deeper into this unexpected B cell behaviour. They discovered that in lymph nodes near the first tumour, B cells were taking antigens from the treated tumour and presenting those antigens to T cells.
Those tumour-specific T cells then travelled to the abscopal tumour to fight the cancer.
The researchers also investigated the addition of an agonistic antibody against OX40. This anti-OX40 further enhanced T cell activation and therapeutic responses. This study holds promise for the antitumour impact of the triple combination of anti-OX40, CpG and IL-12Fc.
“Our data suggest that in the future, the role of B cells should be investigated in other forms of tumour immunotherapy and that agents providing B cell stimulation, such as CpG, IL12-Fc, or B cell-activating antibodies, might be added to T cell stimulating approaches to enhance the potency and specificity of immunotherapeutic regimen,” the authors write.
Written by Poppy Jayne Morgan, Front Line Genomics
Image Credit: Canva
