Immune Checkpoint Inhibitors for Brain Metastases in Non-Small-Cell Lung Cancer: From Rationale to Clinical Application

Abstract

Brain metastases (BM) is common in non-small-cell lung cancer (NSCLC) patients. Immune checkpoint inhibitors (ICIs) have gradually become a routine treatment for NSCLC BM patients. Currently, three PD-1 inhibitors (pembrolizumab, nivolumab and cemiplimab), one PD-L1 inhibitor (atezolizumab) and one CTLA-4 inhibitor (ipilimumab) have been approved for the first-line treatment of metastatic NSCLC. It is still controversial whether PD-L1, tumor infiltrating lymphocytes, and tumor mutation burden can be used as predictive biomarkers for immune checkpoint inhibitors in NSCLC patients with BM. In addition, clinical data on NSCLC BM were inadequate. Here, we review the theoretical basis and clinical data for the application of ICIs in the therapy of NSCLC BM.

Analysis of Immunotherapy Combined with Radiotherapy in Patients with Brain Metastasis of Driver Gene-Negative Non-Small-Cell Lung Cancer

“…Studies have shown that the occurrence of brain metastasis in advanced NSCLC is related to the immune escape of tumors. [ 16 ]. Tumors can interact with the immune system.…”

The Long-Term and Short-Term Efficacy of Immunotherapy in Non-Small Cell Lung Cancer Patients With Brain Metastases: A Systematic Review and Meta-Analysis

“…Firstly, immunotherapy may be preferable over non-immunotherapy for NSCLC patients with BMs, with longer PFS (HR = 0.48) and OS (HR = 0.64). The advantage may be caused by the synergy between immunotherapy and chemotherapy/radiotherapy ( 81 – 86 ). For example, immunotherapy enhanced the radiotherapy-induced abscopal effect and reversed the immunosuppressive effect of radiation, by blocking the immune checkpoint between antigen-presenting cells and lymphocytes in regional lymph nodes and other organs.…”

Immune Subtypes in LUAD Identify Novel Tumor Microenvironment Profiles With Prognostic and Therapeutic Implications

“…Therefore the molecular classifications and therapeutic implications remain to be further studied (8). The expression level of PD-L1 protein on the tumor was reported as a predictive biomarker of poor prognosis of NSCLC (9,10) and clinically benefiting from ICIs (11)(12)(13)(14). PD-L1 is rich in benefits but is an imperfect marker, for the best response rate is still less than 50% in PD-L1 high NSCLC patients.…”

“…PD-L1 is rich in benefits but is an imperfect marker, for the best response rate is still less than 50% in PD-L1 high NSCLC patients. Recently, anti-tumor immunity of LUAD patients (15)(16)(17), tumor immunogenicity (5, 6, 10-12, 16, 18-20), and tumor immune microenvironment (TME) (7,11,14,18,19,21) are also reported to modulate the therapeutic impact of ICIs. Several biomarkers, including tumor mutational burden (TMB) (11), blood tumor mutational burden (bTMB) (22), human leukocyte antigens (HLA) loss-of-heterozygosity (LOH) status (20), and murine double minute 2/4 (MDM2/ MDM4) amplification (23), which could affect the adaptive immune response to the tumors, have been widely studied to be associated with the efficacy of ICI therapy in LUAD patients.…”