A new discovery about how immune cells called B cells work could reshape cancer treatment by enabling the body to mount a targeted defense against tumors in specific organs. Immunologist Joshua Moreau and his team at Oregon Health and Science University (OHSU) have demonstrated that B cells can gather in tissues like skin and lungs, establish permanent residence there, and attack cancer cells on demand. Unlike traditional chemotherapy that affects the entire body, this approach concentrates protection exactly where it's needed.

What Are B Cells and Why Have They Been Overlooked in Cancer Treatment?

For the past decade, T cells have dominated the spotlight in cancer immunotherapy. These white blood cells are the foundation of checkpoint inhibitor drugs, which help the immune system recognize and attack cancer more effectively. But B cells, another type of white blood cell, have quietly circulated in the background, largely ignored by cancer researchers.

"Until very recently, people didn't even think B cells could form residency, and so they've sort of been ignored in the context of tissue biology, tissue immunity and especially in tumor biology and cancer immunology," explained Joshua Moreau, assistant professor in OHSU's Division of Oncological Sciences, Department of Dermatology, and Department of Cell, Developmental and Cancer Biology.

"Until very recently, people didn't even think B cells could form residency, and so they've sort of been ignored in the context of tissue biology, tissue immunity and especially in tumor biology and cancer immunology," said Joshua Moreau.

Joshua Moreau, Assistant Professor, Oregon Health and Science University

This oversight represents a significant gap in cancer immunology. Moreau's curiosity led him to ask a simple but powerful question: what if you could train B cells to recognize cancer and position them as permanent sentries in vulnerable tissues ?

How Did Researchers Train B Cells to Fight Melanoma and Lung Cancer?

Moreau's team used what they call a "teach first, challenge later" approach in mouse models. The process involved several key steps that demonstrate the potential of this vaccination strategy.

• Initial Training: Researchers introduced cancer-associated proteins, called antigens, into mice so their immune systems would learn to recognize them as threats.
• Skin Cancer Test: The team used a laser-assisted skin vaccination to inject melanoma cells expressing those same proteins directly into the skin.
• Lung Cancer Test: In a separate experiment, they used a nasal spray vaccine method to train B cells to defend the lungs, then challenged mice with lung cancer tumor cells.

The results were striking. In both cases, B cells gathered at the injection sites and neutralized the cancer cells. What happened next was even more remarkable: the B cells didn't leave. Months after the initial challenge, these resident B cells remained clustered in the skin and lungs, standing guard against future threats.

How to Understand the Advantages of Localized Immunotherapy

• Targeted Protection: B cells remain in the specific tissue where they're needed, creating a localized defense system rather than a body-wide response.
• Reduced Side Effects: Traditional cancer treatments like chemotherapy cause toxicities and side effects throughout the body, but this vaccination method concentrates its effects only where treatment is necessary.
• Long-Term Memory: Resident B cells maintain their vigilance for months, providing ongoing protection against cancer recurrence in that specific location.
• Tissue-Specific Adaptation: B cells in the skin become exquisitely tuned to that environment's biology, making them more effective at regulating tissue health and tackling disease challenges specific to that location.

"The fact that these B cells don't recirculate and they're sort of exquisitely tuned to that particular environment is notable. So, if it's the skin, these memory resident cells are better able to work in that environment and regulate the biology of that tissue. And then if a disease comes along, whether that's a pathogen or cancer, they're best able to actually tackle that challenge," said Moreau.

Joshua Moreau, Assistant Professor, Oregon Health and Science University

Moreau emphasized that the localized nature of this approach represents a fundamental shift in how we might treat cancer. "More traditional cancer treatments, like chemotherapy, can cause toxicities and side effects that are difficult to deal with, but with this method, it's concentrated, not systemic. It's working where it needs to work and not anywhere else," he noted.

Moreau

When Might This Treatment Reach Patients?

While the early results are encouraging, Moreau and his team are proceeding with appropriate caution. The research is still in the preclinical stage, with experiments conducted in mouse models. The team is currently preparing their findings for publication in a scientific journal, but significant work remains before this approach could be tested in humans.

"What works in mice doesn't always work in humans, and the road from bench to bedside can be long," Moreau cautioned. However, he emphasized that every scientific step matters. "Small discoveries can add up to a big breakthrough," he added.

The research has broader implications beyond melanoma and lung cancer. In February 2024, Moreau was the senior author of a journal publication describing how B cells organize, mature, and adapt in cases of hidradenitis suppurativa, a chronic skin disease that causes painful lesions. This demonstrates that understanding B cell behavior has applications across multiple skin conditions and diseases.

Why Does This Research Matter for the Future of Cancer Care?

Moreau's work represents a paradigm shift in cancer immunology. For years, researchers focused almost exclusively on T cells and checkpoint inhibitors because those mechanisms were well understood. B cells, by contrast, have been underexplored in the context of cancer, despite their proven ability to mount powerful immune responses.

"It's incredibly rewarding to think that work I'm doing could one day help people with skin conditions or skin cancer. It's why I like to focus on the basic biology of what we've been working on. The drug that has helped me so much stems from fundamental immunology, from how immune responses are regulated. And that is basically what we're trying to do with B cells," said Moreau.

Joshua Moreau, Assistant Professor, Oregon Health and Science University

Moreau's personal experience with severe eczema, which was eventually treated with a biologic therapy that harnesses the immune system, informs his research philosophy. He believes that understanding the fundamental biology of immune responses, rather than rushing to applications, is the path to meaningful breakthroughs.

The research has been supported by funding from the Melanoma Research Alliance Young Investigator Grant, The LEO Foundation, The Elsa U. Pardee Foundation, and startup funds from the Knight Cancer Institute, reflecting the scientific community's recognition of the work's potential.

As Moreau looks ahead, he remains focused on the bigger picture. "Could this, down the road, be a situation where a patient has a tumor, and you can deliver this localized vaccination method to eliminate it? Maybe. But more broadly, we're contributing to the understanding of the players involved in a localized tumor or tissue disease and how they interact with each other. How can we use that knowledge to unlock the full capability of the immune system to target the cancer?" he concluded.