Mechanisms underlying success and failure of cancer immunotherapy

Beyranvand Nejad, E.

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....Show moreIn 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.Show less

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Mechanisms underlying success and failure of cancer immunotherapy

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