Improving anti-tumour immunity by combining brain immunology and immunotherapy in brain Tumours

Abstract

Brain tumours are one of our biggest challenges in oncology because of where they reside in the body and their presence in the complex immunosuppressive microenvironment of the central nervous system. It has been recognized that immunotherapy represents a new dimension to treating such tumours by activating the host immune system against malignant tumour cells. Despite that, brain tumours have shown limited responsiveness to single-agent immunotherapy, thus suggesting the need for combination strategies that could effectively enhance anti-tumour immunity. The present review examines the progress made on combination immunotherapy strategies that aim to improve immune function against brain tumours. In this page; we have detailed the different combination strategies of immune checkpoint inhibitors, adoptive cell therapy, vaccines, and targeted therapies with immune modulatory agents. These combination strategies are intended to protect against the immune suppressive hurdles associated with the brain TME and enhance potent and sustained anti-tumour immunity. In addition, we review preclinical and clinical studies that investigate the efficacy and safety of these combination strategies in both brain tumour models and patients. Although some of the combinations have demonstrated promising results in preclinical studies, translating them into clinical benefits is challenging. Challenges and future perspectives on combination immunotherapy in brain tumours-clinical effectiveness of anti-PD-1 therapy and reasons underlying suboptimal therapeutic benefit over mono therapy in patients with a brain tumour (off-target effects, treatment-related toxicities, and patient heterogeneity).