Personalized Oncology Meets Immunology: The Path toward Precision Immunotherapy

Abstract

Personalized oncology aims to tailor therapy by targeting the unique genetic characteristics of a patient's tumor, whereas cancer immunotherapy focuses on activating the patient's immune system to control the tumor. The fusion of these ostensibly separate strategies has created a new dimension for personalized cancer immunotherapy. This entails the development of next-generation cancer vaccines that target neoantigens as well as the use of mutational signatures as predictive biomarkers for clinical response. The optimal use of immunotherapeutic agents will hinge on a robust understanding of the mutational profile of a cancer's genome that significantly dictates antitumor immunity and immunotherapeutic response.

Significance: Cancer immunotherapy has provided substantial clinical benefit in a significant number of patients with advanced disease. However, the need for more precise immunotherapies and predictive biomarkers remains pressing. Recent progress in these areas has been promising and has created a framework for precision immune-oncology. Cancer Discov; 6(7); 703-13. ©2016 AACR.

Conflict of interest statement

Disclosure of Potential Conflicts of Interest: T.A. Chan is a cofounder of Gritstone Oncology; No potential conflicts of interest for R.M.

©2016 American Association for Cancer Research.

Figures

Figure 1. Immunoregulatory influences within the tumor microenvironment

Stimulatory (green) and inhibitory (red) signals between T-lymphocytes and antigen presenting/tumor cells are depicted above. Drugs in clinical investigation stimulating or inhibiting these specific targets are also illustrated.

Figure 2. Strategies for personalized precision immunotherapy

After biopsy of the patient’s tumor, whole exome sequencing permits characterization of the tumor genome and identification of predicted neoantigens. This patient-specific information can then be utilized to individualize immunotherapy care against tumor-specific vulnerabilities.