Survival of
gastrointestinal cancer remains dismal, especially for metastasized disease. For various
cancers, especially
melanoma and
lung cancer,
immunotherapy has been proven to confer survival benefits, but results for
gastrointestinal cancer have been disappointing. Hence, there is substantial interest in exploring the usefulness of adaptive immune system education with respect to anti-
cancer responses though vaccination. Encouragingly, even fairly non-specific approaches to vaccination and immune system stimulation, involving for instance
influenza vaccines, have shown promising results, eliciting hopes that selection of specific
antigens for vaccination may prove useful for at least a subset of
gastrointestinal cancers. It is widely recognized that immune recognition and initiation of responses are hampered by a lack of T cell help, or by suppressive
cancer-associated factors. In this review we will discuss the hurdles that limit efficacy of conventional
cancer therapeutic vaccination methods (e.g.,
peptide vaccines, dendritic cell vaccination). In addition, we will outline other forms of treatment (e.g.,
radiotherapy,
chemotherapy, oncolytic viruses) that also cause the release of
antigens through immunogenic
tumor cell death and can thus be considered unconventional vaccination methods (i.e., in situ vaccination). Finally, we focus on the potential additive value that vaccination strategies may have for improving the effect
immunotherapy. Overall, a picture will emerge that although the field has made substantial progress, successful
immunotherapy through the combination with
cancer antigen vaccination, including that for
gastrointestinal cancers, is still in its infancy, prompting further intensification of the research effort in this respect.