The Role of Immune Checkpoint Inhibition in the Treatment of Brain Tumors

Abstract

The standard of care for malignant gliomas of the brain has changed very little over the last few decades, and does not offer a cure for these rare, but fatal, tumors. The field of immunotherapy has brought potent new drugs into the oncological armamentarium, and is becoming recognized as a potentially important arm in the treatment of glioblastoma for adults. Immune checkpoints are inhibitory receptors found on immune cells that, when stimulated, cause those immune cells to become quiescent. While this is a natural mechanism to prevent excessive inflammatory damage and autoimmunity in otherwise healthy tissues, cancer cells may utilize this process to grow in the absence of targeted immune destruction. Antibodies derived to block the stimulation of these negative checkpoints, allowing immune cells to remain activated and undergo effector function, are a growing area of immunotherapy. These therapies have seen much success in both the preclinical and clinical arenas for various tumors, particularly melanoma and nonsmall-cell lung cancer. Multiple clinical trials are underway to determine if these drugs have efficacy in glioblastoma. Here, we review the current evidence, from early preclinical data to lessons learned from clinical trials outside of glioblastoma, to assess the potential of immune checkpoint inhibition in the treatment of brain tumors and discuss how this therapy may be implemented with the present standard of care.

Current State and Future Prospects of Immunotherapy for Glioma

“…Preclinical studies are investigating the potential of other checkpoints such as TIM-3, IDO, LAG-3 and adenosine A2a receptor as therapeutic targets in glioma [144]. Combination of anti-PD-1, anti-TIM-3 and focal radiation resulted in regression of murine gliomas and combination of IDO, CTLA-4 and PD-L1 blockade induced longterm survival in 100% of the glioma-bearing animals [145,146].…”

Specific clinical and immune features of CD68 in glioma via 1,024 samples

“…The results showed that CD68 expression had a strong correlation with CD163, CD11b, CD14, and CD204, suggesting that CD68 and these markers played a synergistic role in tumor inflammatory response to promote tumor progression and metastasis. Emerging data showed that the development of monoclonal antibodies to block immune checkpoints is a promising treatment for glioma 34. Moreover, we analyzed the relationship between CD68 and immune checkpoints.…”

Impact of General Factors on Glioma Immunotherapy

“… 6 Moreover, other inhibitory and stimulatory immune checkpoints exist, including T-cell immunoglobulin and mucin-domain-containing 3 (Tim-3), indoleamine 2,3-dioxygenase, T-cell immunoreceptor with Ig, ITIM domains, 4-1BB, and OX40 (also known as CD134). 7 8 9 10 …”