For immunologists, it has become clear that immunotherapeutic strategies should engage multiple effector mechanisms to overcome the immunosuppressive mechanisms of cancer. For patients with metastatic cancer or larger burden of disease, a single therapeutic agent is unlikely to be effective, and immunotherapy should be combined with conventional cancer treatments, with the aim of not only to reduce tumor load, but also to abrogate immune tolerance and to enhance anticancer immune responses (Table 3 and Figure 1). This opens a field for fundamental and clinical research to better develop the concept of chemoimmunotherapy, especially to design the optimal choice, schedule and dose of therapeutic associations. As the success of these combined approaches may rely on the crosstalk between cancer cells, tumor stroma and the patient's immune system, three major considerations appear crucial for implementation of chemoimmunotherapy efficient combinations. First, cancer-bearing patients who may benefit from such combinations must be properly selected using appropriate biomarkers, which underscores the crucial need for predictive biomarkers that can be introduced in the clinical routine. Second, the optimal choice of combinations along with the schedule and dosage of administration of each component of the chemoimmunotherapy treatment remain to be determined, which highlights the need to develop clear immune biological and clinical parameters that allow for rapid go/no-go decisions. Finally, it is important to keep in mind that cancer patients are often heavily co-medicated with a number of drugs for symptom management as well as over-the-counter products and supplements, which can also affect the immune system. Future research and clinical trials that will rationally sequence immunomodulators, cancer vaccines and conventional treatments of cancer will benefit from taking into account these important aspects.
Ann Oncol. 2015;26(9):1813-1823. © 2015 Oxford University Press
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