Immunity to the Melanoma Inhibitor of Apoptosis Protein (ML-IAP; livin) in Patients with Malignant Melanoma

DSpace/Manakin Repository

Immunity to the Melanoma Inhibitor of Apoptosis Protein (ML-IAP; livin) in Patients with Malignant Melanoma

Citable link to this page

 

 
Title: Immunity to the Melanoma Inhibitor of Apoptosis Protein (ML-IAP; livin) in Patients with Malignant Melanoma
Author: Yuen, Noah K.; Zhan, Qian; Velazquez, Elsa F.; Giobbie-Hurder, Anita; Zhou, Jun; Murphy, George Francis; Hodi, Frank Stephen

Note: Order does not necessarily reflect citation order of authors.

Citation: Zhou, Jun, Noah K. Yuen, Qian Zhan, Elsa F. Velazquez, George F. Murphy, Anita Giobbie-Hurder, and F. Stephen Hodi. 2011. Immunity to the melanoma inhibitor of apoptosis protein (ML-IAP; livin) in patients with malignant melanoma. Cancer Immunology, Immunotherapy 61(5): 655-665.
Full Text & Related Files:
Abstract: Therapeutic targeting of melanoma antigens frequently focuses on the melanocyte differentiation or cancer-testis families. Antigen-loss variants can often result, as these antigens are not critical for tumor cell survival. Exploration of functionally relevant targets has been limited. The melanoma inhibitor of apoptosis protein (ML-IAP; livin) is overexpressed in melanoma, contributing to disease progression and treatment resistance. Improved understanding of the significance of ML-IAP immune responses in patients has possible therapeutic applications. We found ML-IAP frequently expressed in melanoma metastases by immunohistochemistry. To assess spontaneous immunity to ML-IAP, an overlapping peptide library representing full-length protein was utilized to screen cellular responses in stage I–IV patients and healthy controls by ELISPOT. A broad array of \(CD4^+\) and \(CD8^+\) cellular responses against ML-IAP was observed with novel class I and class II epitopes identified. Specific HLA-A*0201 epitopes were analyzed further for frequency of reactivity. The generation of specific \(CD4^+\) and cytotoxic T cells revealed potent functional capability including cytokine responsiveness to melanoma cell lines and tumor cell killing. In addition, recombinant ML-IAP protein used in an ELISA demonstrated high titer antibody responses in a subset of patients. Several melanoma patients who received CTLA-4 blockade with ipilimumab developed augmented humoral immune responses to ML-IAP as a function of treatment which was associated with beneficial clinical outcomes. High frequency immune responses in melanoma patients, associations with favorable treatment outcomes, and its essential role in melanoma pathogenesis support the development of ML-IAP as a disease marker and therapeutic target.
Published Version: doi:10.1007/s00262-011-1124-1
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3337996/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10361991
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters