Immunotherapy in Gastrointestinal Carcinoma - How to Separate Hope from Hype

time, the infection is asymptomatic. In intermittent cases, the emergence of lymphoma, gastric, or head and neck carcinoma is evoked. Typically, the EBV lytic replication (the process that generates new virus paricles) is a strong risk factor for these cancer types. Most recently, a new mechanism was identified by which EBV particles can induce chromosomal instability without establishing a chronic infection, thereby conferring a risk for development of tumors that do not necessarily carry the viral genome. In detail, the EBV viral protein BNRF1 induced centrosome amplification, but BNRF1-deficient viruses largely lost this property [9]. – Do we have here a new marker for chromosomal instability and potential immunogenic tumors that is not yet known? All in all, there are exciting times ahead for us as clinical scientists and as practitioners. As we were able to show in our publications, the immune system is a rather gifted therapeutic partner in combination with chemotherapy, irradiation, or other innovative strategies. We have great hopes for new immunotherapy combinations with classical treatment strategies – even if we might not yet fulfil every patient’s expectations. In the last article of this series [8], we discuss tumor associated macrophages (TAM); myeloid derived suppressor cells (MDSC) as well as regulatory T cells (Tregs) as new immunotherapeutic targets. In addition, we describe how blockade of the GITR, IDO, Csf1R, or WNT signaling pathways offers capable approaches for overcoming the immune silencing within the non-responsive or resistant tumor microenvironment. The meticulous assessment of the genetic background and our biomarker panels will help us to separate real hope from hype. These new studies give us a common challenge and new perspectives for our patients.