In another Nature study of individuals with melanoma or RCC, Dr Wargo and her team performed bulk RNA sequencing and found that responders to immune checkpoint blockade had distinct B-cell markers.4 “We demonstrated that B cells seem to be integral to responses to cancer immunotherapy,” said lead author Beth Helmink, MD, PhD, surgical oncology fellow at MD Anderson. The research showed B cells were also localized within tertiary lymphoid structures. “The next question we wanted to answer was, ‘What were these B cells doing?’ It looks like B cells are helping the T cells be more active by forming lymph node-like structures inside the tumors themselves and may be producing antibodies that are contributing to the response to immune checkpoint blockade,” she said.

The 3 papers are a valuable contribution to the literature and hopefully will encourage more research interest in B cells, noted Tullia Bruno, PhD, an immunologist at UPMC Hillman Cancer Center in Pittsburgh, Pennsylvania, who was invited by Nature to write an editorial on the research.5 “I trained on T cells, but as someone who’s crossed over to B cells, I think it’s important to focus on other cells that modulate the immune response. It’s an underdeveloped field,” she said.

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According to Dr Bruno, the authors found a correlation between the presence of B cells — as well as the structures that contain B cells — and treatment response. “That’s the real strength of these studies, and that’s why we should pay attention to them. They show that patients are doing better,” she said.

The studies are also valuable because they address the relationship between B cells and T cells. “That’s really exciting. It means that if we can continue to boost T-cell activity by manipulating the internal immune system of an individual, we can make more comprehensive and improved treatments,” said Dr Bruno. She added that she hopes more attention to and research on B cells will solve the mystery of why only 20% to 30% of patients respond to immunotherapies. “People don’t know what the missing pieces are, but we’ve been thinking about them in a very T-cell–centric way,” said Dr Bruno.


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Bruno also emphasized she believes that studying the interplay between B cells and T cells will lead to the next wave of progress in cancer therapy development. “As a field, there’s been a big push not to consider components of the immune system in a siloed way,” she said. “We want to see how they all come together.”

Disclosure: Some of the study authors across the cited papers disclosed financial relationships with research institutions, pharmaceutical companies, and medical device companies. For a full list of disclosures, please refer to the original studies.

References

  1. Petitprez F, de Reyniès A, Keung EZ, et al. B cells are associated with survival and immunotherapy response in sarcoma. Nature. 2020;577(7791):556–560.
  2. ClinicalTrials.gov. Sarcoma Alliance for Research through Collaboration. (2014). SARC028: A Phase II Study of the Anti-PD1 Antibody Pembrolizumab (MK-3475) in Patients With Advanced Sarcomas. NCT02301039. https://clinicaltrials.gov/ct2/show/NCT02301039. Accessed February 24, 2020.
  3. Cabrita R, Lauss M, Sanna A, et al. Tertiary lymphoid structures improve immunotherapy and survival in melanoma.  Nature. 2020;577(7791):561–565.
  4. Helmink BA, Reddy SM, Gao J et al. B cells and tertiary lymphoid structures promote immunotherapy responseNature. 2020;577(7791):549–555.
  5. Bruno TC. New predictors for immunotherapy responses sharpen our view of the tumour microenviroment. Nature. 2020;577(7791):474-476.