Immune checkpoint blockade combined with chemotherapy may sensitize tumors that are not infiltrated by immune cells, which are often referred to as “cold” tumors, to treatment with immune checkpoint blockade, a review article published online in the Annals of Oncology concluded.1

The review authors evaluated data from both preclinical studies and ongoing clinical trials and described the effects of different chemotherapeutic agents and potential value of immunochemotherapy combinations. They also evaluated data based on different dosing schedules.

Although chemotherapeutic agents were originally thought to suppress the immune system, preclinical studies have shown that chemotherapeutic agents actually have immunostimulatory effects, and this property, when combined with immune checkpoint blockade, could improve tumor response to therapy. Chemotherapeutic agents are thought to stimulate the immune system by increasing immunogenicity and T-cell infiltration. Chemotherapies are also thought to boost responses to subsequent therapy because they can hinder immunosuppressive cells and/or promote effector cells.

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“Each chemotherapeutic drug impacts the tumor microenvironment differently,” the review authors wrote. “In order to determine the most suitable combination partners for ICB [immune checkpoint blockade], it is crucial to understand these mechanisms.”

The review authors proposed that combining immune checkpoint blockade with different chemotherapeutic agents could improve the immunological features of the tumor microenvironment and in turn, improve tumor response to immunotherapy, resensitizing tumors that have historically been unresponsive. They cautioned that the timing, dose amount, and sequence of certain chemotherapeutic agents and immunotherapeutics is important and could affect outcomes.

“Further studies should focus on determining the optimal drug combinations, sequence effects, and optimal concentration-time profiles in representative preclinical models,” the review authors wrote.

Reference

  1. Heinhuis KM, Ros W, Kok M, Steeghs N, Beijnen JH, and Schellens JHM. Enhancing anti-tumor response by combining immune checkpoint inhibitors with chemotherapy in solid tumors [published online January 4, 2019]. Ann Oncol. doi: 10.1093/annonc/mdy551