Kevin Ng, a researcher studying the promotion of immunotherapy of lung cancer by antibodies against endogenous retroviruses, joins Immune and discusses his work. They explore the role of endogenous retroviruses in the immune system and the development of a mouse model for studying lung cancer. They also delve into the functionality of B cells in tumor protection, the role of PD1 and PDL1 in regulating the immune response, and using gene sequencing and baseline data to predict cancer response.
Tertiary lymphoid structures and B cell responses play a significant role in lung cancer immunotherapy.
Different histological subtypes of lung cancer exhibit variations in immunogenicity, impacting the effectiveness of immunotherapy approaches.
Understanding the role of endogenous retroviruses in stimulating B cell responses and the formation of tertiary lymphoid structures may lead to new targeted treatments for lung cancer.
Deep dives
The Role of Tertiary Lymphoid Structures in Lung Cancer Immunotherapy
Tertiary lymphoid structures (TLS) within lung cancer tissue have been associated with improved patient survival. Within these TLS, B cells organize into germinal center-like structures, and the presence of these structures correlates with a stronger B cell response and the production of antibodies. As a mouse model, a lung cancer cell line expressing endogenous retroviruses was used. The mice developed TLS containing B cells and exhibited an antibody response against the tumor. Additionally, antibody transfer experiments showed that serum from these mice could protect against tumor growth. In human patients with adenocarcinoma, the transcription of endogenous retrovirus envelope proteins was observed, and this correlated with the presence of TLS. PDL1 blockade, a commonly used immunotherapy approach, led to an expansion of B cell responses in both the mouse model and human patients. These findings suggest that B cell responses and the presence of TLS, possibly mediated by endogenous retroviruses, play a significant role in lung cancer immunotherapy.
Differences in Immunogenicity Among Lung Cancer Subtypes
Different histological subtypes of lung cancer, such as adenocarcinoma and squamous cell carcinoma, exhibit variations in immunogenicity. For instance, adenocarcinoma is characterized by the presence of tertiary lymphoid structures, antibody production, and the expression of endogenous retrovirus envelope proteins. On the other hand, squamous cell carcinoma does not show these features to the same degree. While the exact reasons for these differences are unclear, the variations in immunogenicity could influence the effectiveness of immunotherapy approaches. Adenocarcinomas, with their stronger B cell responses and immunogenic characteristics, tend to respond better to immunotherapies targeting PD-1/PD-L1 interactions.
Clinical Implications and Future Research Direction
The findings from both animal models and human patients highlight the importance of B cell responses and the presence of tertiary lymphoid structures in the context of lung cancer immunotherapy. Understanding the role of endogenous retroviruses in stimulating B cell responses and the formation of TLS may provide new opportunities for developing targeted treatments. Further research is needed to explore the specific mechanisms underlying the immunogenicity differences observed in different lung cancer subtypes. Additionally, investigating the potential synergy between immunotherapies and other treatment modalities, such as K-Ras inhibitors, could lead to improved outcomes for patients. Overall, these findings offer insights into the complex interplay between the immune system and lung cancer, paving the way for more effective therapeutic strategies.
The Role of B Cells in Tumor Control
The podcast episode explores the understudied role of B cells in tumor control. It highlights the importance of studying B cell responses to self-antigens in the context of tumor microenvironments. The episode emphasizes that tumors are not viruses and that understanding the interactions between B cells and tumors is crucial for developing effective cancer treatments.
The Significance of Endogenous Retroviruses in the Immune Response
The podcast delves into the significance of endogenous retroviruses (ERVs) in the immune response against cancer. It explains that ERVs, which are typically ignored in traditional tumor sequencing, can play a crucial role in anti-tumor antibody responses. The episode highlights the upregulation of the envelope protein of a specific ERV in tumors and its potential as a therapeutic target. It also discusses the challenges and potential future directions for studying ERVs in cancer immunology.
