A Pilot Study to Evaluate the Safety of a 3 Weeks Sitagliptin Treatment in HCC Patients Undergoing Liver Resection
Status:
Completed
Trial end date:
2018-09-01
Target enrollment:
Participant gender:
Summary
Boosting of tumor cell killing by cytotoxic lymphocytes may be a promising means to enhance
anti-tumor immunity. Prior studies demonstrated that tumor infiltration by cytotoxic
lymphocytes correlates with control of tumor growth and is associated with an improved
prognosis in cancer patients. Trafficking of activated lymphocytes is a tightly regulated
mechanism and the specific nature of the chemokine milieu is a crucial determinant for
permitting T cell entry into the tumor microenvironment. CXCL10 is an interferon-inducible
chemokine particularly important for the recruitment of activated T, and it has been shown to
enhance anti-tumor responses through its action on cytotoxic T cells (e.g., glioblastoma,
colorectal adenocarcinoma and lung carcinoma). Additionally, roles for CXCL10 as an
anti-tumor effector include its ability to chemo-attract NK cells into sites of inflammation,
and its ability to inhibit development of new vasculature and induce the regression of newly
formed vessels. Adding a layer of complexity, the function of CXCL10 can be regulated by
dipeptidylpeptidase IV (DPPIV), leading to the formation of a dominant negative, antagonist
form of the chemokine. This was initially demonstrated in vitro, and recent work has provided
convincing in vivo evidence that antagonist forms of CXCL10 regulate lymphocyte trafficking.
The main goal of this protocol is to evaluate the tolerance of sitagliptin treatment in HCC
patients, and secondary DPPIV inhibitors as a strategy for protecting CXCL10 chemokine
agonist activity as a means to enhance tumor regression.