Prospect of immunotherapy alone in patients with advanced NSCLC with high btmb: a review and a meta-analysis

In the current era of precision medicine, the management of patients with brain metastases (BMs) is rapidly evolving. The technical evolution of radiotherapy, now able to offer focal ablative treatments, in combination with new systemic target therapies, is changing the therapeutic landscape in this challenging clinical setting. Moreover, the emerging role of the tumor microenvironment in influencing the response to standard therapies is revealing new potential prognostic and predictive biomarkers for patients with BMs. In this review, we offer an overview of the current trends in the treatment of BMs from lung cancer, with a secondary focus on future perspectives based on integrated translational approaches.

Non-small-cell lung cancer (NSCLC) remains one of the leading causes of death worldwide. While NSCLCs possess antigens that can potentially elicit T cell responses, defective tumor antigen presentation and T cell activation hinder host anti-tumor immune responses. The NSCLC tumor microenvironment (TME) is composed of cellular and soluble mediators that can promote or combat tumor growth. The composition of the TME plays a critical role in promoting tumorigenesis and dictating anti-tumor immune responses to immunotherapy. Dendritic cells (DCs) are critical immune cells that activate anti-tumor T cell responses and sustain effector responses. DC vaccination is a promising cellular immunotherapy that has the potential to facilitate anti-tumor immune responses and transform the composition of the NSCLC TME via tumor antigen presentation and cell–cell communication. Here, we will review the features of the NSCLC TME with an emphasis on the immune cell phenotypes that directly interact with DCs. Additionally, we will summarize the major preclinical and clinical approaches for DC vaccine generation and examine how effective DC vaccination can transform the NSCLC TME toward a state of sustained anti-tumor immune signaling.

作者：刘树伟 山东大学医学院