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.