In the clinic, several
forms of immunotherapy are combined with the standard treatments, including
chemotherapy. Translational studies trying to understand the different outcomes
in patients have led to new questions and hypotheses. The studies described in
this thesis are to answer some of these questions. We revealed the
immunostimulatory effect of the chemotherapy agent; cisplatin. Next, we studied
the mechanism of relapse following immunotherapy with HPV16 SLP vaccination in
mice. We demonstrated that unsuccessful immunotherapy results in immune editing
and secondary resistance. To overcome this, the combination therapies are
required. Moreover, we showed the importance of IL-6 producing by tumors in
dampening anti-tumor response. To induce a long-term sustained effector T cell
response, we examined the potency of mouse cytomegalovirus as a viral
vector-based vaccine. We demonstrated that the demarcated thresholds of
vaccine-specific T cells correlate to tumor protection. Recognizing the fact
that at each phase of the antitumor immune response a different type of help
might have to be provided to obtain maximal therapeutic efficacy, the correct
timing of various types of chemotherapeutic agents or immune modulators when
used in combination is discussed. Finally, we discussed the general aspects and
relevance of the studies mentioned in this thesis.Greiner Bio-One B.V.LUMC / Geneeskund
