A recent study conducted by Dr. Shira Tabachnick-Cherny and her team has shed light on a potential roadblock to the effectiveness of immunotherapy in certain cancer patients. While previous research has shown that higher numbers of CD8+ T cells in the tumors of patients with Merkel cell carcinoma (MCC) correlated with better outcomes, it remained unclear why some patients with abundant T cells did not respond to immunotherapy.
Dr. Tabachnick-Cherny’s investigation focused on the role of myeloid cells, a type of immune cell that can either enhance or suppress T cell responses. Analyzing samples from MCC patients prior to immunotherapy, the researchers discovered that macrophages, a specific type of myeloid cell, were the dominant immune cell found in the tumors. Macrophages are known to play a role in alerting other immune cells to invading pathogens, but in tumors, they often suppress immune responses.
Collaborating with the Fred Hutch Experimental Histopathology Core, the team analyzed the macrophages and T cells in samples from MCC patients who had received immunotherapy with varying responses. They found that patients who showed the best responses to immunotherapy had high levels of T cells but few macrophages in their tumors. On the other hand, patients who had an abundance of T cells but still experienced disease progression on immunotherapy had a high presence of macrophages. This suggests that macrophages might be inhibiting T cell responses to immunotherapy.
Interestingly, the researchers observed that the number of macrophages near T cells did not differ significantly between patients who responded and those who progressed on immunotherapy. This implies that macrophages may hinder T cell function by secreting immunosuppressive molecules into tumors, rather than through direct interactions.
These crucial findings pave the way for future investigations into targeting macrophages as a potential strategy to improve immunotherapy outcomes for patients who do not respond to treatment. Dr. Nghiem, the lead researcher, highlights the importance of these discoveries: “There are several therapeutic approaches […] that may make sense to consider based on these findings.” For instance, ongoing clinical trials involving anti-LILRB drugs show promise in targeting macrophages and benefiting MCC patients.
Moreover, future therapeutic approaches aimed at combating immune evasion and resistance to immunotherapy in other cancer types involving macrophages may also benefit from these insights.
Frequently Asked Questions (FAQ)
1. What is immunotherapy?
Immunotherapy refers to a type of treatment that uses the body’s own immune system to fight diseases, particularly cancer. It works by stimulating or boosting the immune system’s natural ability to recognize and target cancer cells.
2. What are myeloid cells?
Myeloid cells are a group of immune cells involved in the innate immune response. They include cells such as macrophages, dendritic cells, and granulocytes. Myeloid cells play important roles in inflammation, immune regulation, and defense against pathogens.
3. What are macrophages?
Macrophages are a type of white blood cell that engulfs and digests foreign substances, microbes, cancer cells, and cellular debris. They are critical in the immune response and act as scavengers, clearing out damaged cells and promoting tissue repair.
4. What is Merkel cell carcinoma (MCC)?
Merkel cell carcinoma is a rare and aggressive skin cancer that typically arises on sun-exposed areas of the body. It is caused by a virus known as the Merkel cell polyomavirus. Immunotherapy has shown promise in treating MCC, but not all patients respond to this type of treatment.
5. How might targeting macrophages improve immunotherapy outcomes?
The study suggests that macrophages can act as a roadblock to the effectiveness of immunotherapy by suppressing T cell responses. Targeting and inhibiting these macrophages could potentially enhance the immune response, leading to improved outcomes in patients who do not initially respond to immunotherapy. Ongoing clinical trials with anti-LILRB drugs show potential in targeting macrophages in MCC patients.