The Promiseshutterstock_177372503.jpg of Immunotherapy and Early Successes

Our immune systems may be one of the most powerful resources that we have in the fight against cancer. With all of the mounting evidence of immunotherapy used to treat melanoma, lung cancer and bladder cancer, immunotherapy as a treatment option is here to stay. But as highlighted on many occasions and again at ASCO [1], immunotherapy doesn’t always work.

Understanding Why Immunotherapy Doesn’t Always Work

While there’s certainly a scientific revolution going on, we're still in the early stages. For a majority of patients, immunotherapy doesn’t work for reasons that we are trying to better understand. There are many hypotheses as to why, including whether or not the tumor is “hot” or “cold.” “Hot” tumors are those that can be more easily recognized and successfully attacked by the body’s immune system, while “cold” tumors are those that are not. Understanding what makes a tumor responsive to immunotherapy is essential, but very challenging as the tumor biology is dynamic and complex. For instance, while many tumors are “hot” because of their mutational load, there are many tumors with high mutational load that are non-responsive to immunotherapy because of other factors, such as the tumor microenvironment. 

A Path Forward to Providing Individualized Treatments

So how do we make a “cold” tumor “hot”? Having a holistic framework that incorporates the many factors that drive treatment success is a key part of the solution. This framework can involve a characterization of the many aspects that govern how the immune system interacts with tumors [2], including checkpoint inhibition and the degree of mutational load. The framework can also be used to identify how different treatment options address the immune-tumor interaction. Application of this framework will then be a way to better understand whether the treatment for a given cancer patient with her own particular oncologic signature should be single agent immunotherapy, a combination of immunotherapeutic agents, immunotherapy combined with chemotherapy/vaccine, or other emerging options. While limiting medical and financial toxicities, it will enable a purposeful and planned approach for providing an improved chance of success for each individual patient. 

Opportunities for Continued Partnerships

This framework can also serve as a map to systematically allow the scientific and medical communities, in partnership with pharmaceutical and diagnostic companies, to continue the research and commercialization required to ultimately allow each patient to receive the right therapy. A comprehensive understanding based on a holistic framework that characterizes immune-tumor interactions will uncover the best treatments for individuals and will give us a key tool needed to defeat cancer.


[1] R. Vonderheide, “The View Behind Single-Agent Checkpoint Blockade,” ASCO, 2016.

[2] C. Blank et al., “The Cancer Immunogram,” Science, vol 352, pp. 659-660, 2016.

Topics: Nisha Gilra, ASCO, immunotherapy, ASCO2016