by In a recent study published in the journal Cancer Immunology Research, researchers at Vanderbilt University Medical Center have discovered that tumor antigens play a crucial role in improving the effectiveness of cancer immunotherapies. The study, led by Mary Philip, MD, Ph.D., a cancer specialist at Vanderbilt, focused on understanding the complex interactions between immune and tumor cells to develop better strategies for cancer treatment.
Cancer immunotherapies, such as immune checkpoint blockade (ICB), have shown promise in treating cancer by unleashing the body’s own immune system to attack tumor cells. However, the efficacy of these therapies can vary greatly among patients. To address this issue, Philip and her team explored how the type of tumor antigen and the tumor context influence the response of CD8+ T cells, a type of immune cell that plays a crucial role in fighting cancer.
Tumors carry two different types of antigens. Tumor-specific antigens are unique to the tumor cells and are not present in normal tissue, while self/shared antigens are also found in healthy tissue. The study revealed that CD8+ T cell responses differ depending on the type of tumor antigen encountered. While CD8+ T cells recognizing tumor-specific antigens lost their function over time, those recognizing self/shared antigens not only lost their function but also rapidly disappeared from the liver tumors being studied.
Interestingly, the team found that self/shared antigen-specific CD8+ T cells persisted long-term in the spleen but remained dysfunctional. The researchers also discovered that the strength of the T cell receptor signal, which measures the affinity of T cells for their antigens, is crucial for their function. Both too high and too low affinity resulted in dysfunction or no response at all.
Furthermore, the study highlighted the importance of priming CD8+ T cells with inflammatory and infection-induced cytokines in the presence of immune checkpoint blockade for a more effective response. The team observed that CD8+ T cells became dysfunctional when exposed to a tumor, but remained functional when confronted with an acute infection.
Based on their findings, Philip and her team are working on developing strategies to modulate antigen context and affinity in mouse cancer models to enhance anti-tumor CD8+ T cell responses. The goal is to develop immunotherapies that target and kill tumor cells specifically without damaging healthy tissue in patients.
This research provides valuable insights into the mechanisms underlying the response to cancer immunotherapies and opens up new possibilities for improving their effectiveness. By better understanding the role of tumor antigens and their interaction with the immune system, researchers can develop tailored treatments that maximize the immune response against cancer while minimizing side effects.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
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