Near future of tumor immunology: Anticipating resistance mechanisms to immunotherapies, a big challenge for clinical trials

ABSTRACT

The success of immunotherapies brings hope for the future of cancer treatment. Even so, we are faced with a new challenge, that of understanding which patients will respond initially and, possibly, develop resistance. The examination of the immune profile, especially approaches related to the immunoscore, may foretell which tumors will have a positive initial response. Ideally, the mutation load would also be analyzed, helping to reveal tumor associated antigens that are predictive of an effective cytolytic attack. However, the response may be hindered by changes induced in the tumor and its microenvironment during treatment, perhaps stemming from the therapy itself. To monitor such alterations, we suggest that minimally invasive approaches should be explored, such as the analysis of circulating tumor DNA. When testing new drugs, the data collected from each patient would initially represent an N of 1 clinical trial that could then be deposited in large databases and mined retrospectively for trends and correlations between genetic alterations and response to therapy. We expect that the investment in personalized approaches that couple molecular analysis during clinical trials will yield critical data that, in the future, may be used to predict the outcome of novel immunotherapies.

KEYWORDS:

• cancer
• checkpoint blockade
• circulating tumor DNA
• immunoscore
• personalized medicine

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Funding

São Paulo Research Foundation grants (Strauss, B.E) 13/25167–5, fellowships (Catani, J.P.P) 14/11524–3; (Adjemian S.) 12/25380–8.