History will undoubtedly define the last few years as the dawn of immunotherapy for oncology, even though a vision of exploiting our natural defenses to eradicate cancer as an invading enemy, foreign although from inside, dates back over a century. Achievements during the past few years have been remarkable: for the first time, a cancer vaccine has been shown to improve survival; blocking antibodies to the immune checkpoint molecules, cytotoxic T-lymphocyte antigen 4 and programmed death 1, has achieved dramatic benefit across a spectrum of challenging solid and liquid tumors, including apparent cures for advanced melanoma, a cancer that was previously regarded as being as deadly as glioblastoma; and chimeric antigen receptor T cells can induce durable remissions in end-stage leukemia patients. Such results have established immunotherapy as a cornerstone of cancer treatment and have generated great hope in the cancer community of patients, families, and clinicians. Nonetheless, overall efforts to tap the potential of the immune system to effectively attack cancer are in relatively early stages. Durable benefit is limited to subsets of patients, and some types of cancer respond better than others. Unfolding the mysteries underlying variability of response across patients and cancer indications, along with continued development of additional novel immune-based therapeutics, will undoubtedly contribute to the optimal development of immunotherapies for oncology.
Our supplement is designed to provide a timely overview of cancer immunology and immunotherapy as applied to neuro-oncology. There are key factors that distinguish brain cancer patients in this regard. The first article, provided by Gavin Dunn, MD, PhD and Hideho Okada, MD, PhD, provides a foundation to appreciate therapeutic applications described in subsequent articles, by reviewing important considerations regarding the systemic immune system's interaction with the central nervous system. The second article, provided by Drs Edjah Ndoum, Michael Weller, and Amy Heimberger, describes mechanisms employed by cancers to avoid immune system recognition and attack. Unfortunately glioblastomas utilize a host of these immunosuppressive mechanisms, which may abrogate specific immunotherapeutic interventions, particularly when administered as single-agent treatments. The next two articles focus on key applications of immunotherapy currently under extensive clinical evaluation. Duane Mitchell, MD, PhD and John Sampson, MD, PhD review vaccine strategies for neuro-oncology patients followed by a comprehensive review of immune checkpoint targeting agents provided by Drs Michael Lim and William Curry. Although each of these classes of immune therapeutics offers great potential, there is a strong rationale for the development of combinatorial regimens in order to enhance efficacy and diminish the emergence of resistance. Therefore, the final article, by Drs David Reardon, Mark Gilbert, Wolfgang Wick, and Linda Liau, summarizes the rationale and current application of immunotherapy combinatorial regimens.
We are very pleased to bring you this supplement and hope that you find it of value as we move further into the era of immunotherapy for neuro-oncology. We humbly express our deepest gratitude to all of our contributing authors for their hard work along a very tight timeline.
With best wishes,
