MISSION

Westra W, Califano J. Gene expression alterations over large chromosomal regions in cancers include
multiple genes unrelated to malignant progression. Proc Natl Acad Sci USA 2004;101:8715-8720.
Minhas KM, Singh B, Jiang WW, Sidransky D, Califano JA. Spindle assembly checkpoint defects and chromosomal
instability in head and neck squamous cell carcinoma. Int J Cancer 2003;107:46-52.
OZhao M, Rosenbaum E, Carvalho AL, Koch W, Jiang W, Sidransky D, Califano J. Feasibility of quantitative
PCR-based saliva rinse screening of HPV for head and neck cancer. Int J Cancer 2005;117:605-
610.
Sirianni NM, Ha PK, Oelke M, Califano J, Gooding W, Westra W, Whiteside TL, Koch WM, Schneck JP,
DeLeo A, Ferris RL. Effect of human papillomavirus-16 infection on CD8+ T cell recognition of a wild
type sequence p53264-272 peptide in head and neck cancer patients. Clin Can Res 2004;10:6929-
6937.
Wu G, Osada M, Guo Z, Fomenkov A, Begum S, Zhao M, Upadhyay S, Xing M, Wu F, Moon C, Westra
WH, Koch WM, Mantovani R, Califano JA, Ratovitski E, Sidransky D, Trink B. DeltaNp63alpha upregulates
the Hsp70 gene in human cancer. Cancer Res 2005;65:758-766.
Xing M, Westra WH, Tufano RP, Rosenbaum E, Cohen Y, Rhoden KJ, Carson KA, Vasko V, Larin A,
Tallini G, Tolaney S, Holt EH, Hui P, Umbricht CB, Basaria S, Ewertz M, Tufaro AP, Califano JA,
Ringel MD, Zeiger MA, Sidransky D, Ladenson PW. BRAF mutation predicts a poorer clinical prognosis
for papillary thyroid cancer. J Clin Endocrinol Metab 2005;90:6373-6379.
APOPTOSIS OF EFFECTOR T CELLS IN CANCER: IMPLICATIONS FOR IMMUNE THERAPY
Robert L. Ferris, PhD; University of Pittsburgh; YCSA 2003
Based on evidence that HNSCC has been shown to interfere with T cell survival and function, Dr. Ferris
hypothesizes that tumor antigen-specific T cells are preferentially targeted for early apoptosis, leading to
host tolerance to the tumor. This investigation will include a mechanistic study of the dynamic basis for T
cell depletion in patients with HNSCC, its in vivo kinetics, and therapeutic strategies for preventing early
death of circulating immune cells in a prospective series of patients. Results thus far suggest abnormally
high T-lymphocyte apoptosis in cancer. For further documentation, the investigators are initiating a Phase
1 clinical trial where they will directly label T cells from HNSCC patients with deuterated water to compare
cell life to the T cell lifespan in healthy controls. Biomarker analyses from accrued patients and healthy
controls are currently being conducted.
FAMRI Supported Publications
Albers A, Abe K, Hunt J, Wang J, Lopez-Albaitero A, Schaefer C, Gooding W, Whiteside TL, Ferrone
S, DeLeo A, Ferris RL. Antitumor activity of human papillomavirus type 16 E7-specific T cells against
virally infected squamous cell carcinoma of the head and neck. Cancer Res 2005;65:11146-11155.
Albers AE, Ferris RL, Kim GG, Chikamatsu K, DeLeo AB, Whiteside TL. Immune responses to p53 in
patients with cancer: enrichment in tetramer+ p53 peptide-specific T cells and regulatory CD4+CD25+ T
cells at tumor sites. Cancer Immunol Immunother 2005;54:1072-1081.
Kim J, Ferris RL, Whiteside TL. CCR7 protects T lymphocytes from apoptotic cell death in patients
with head and neck cancer. Clin Cancer Res 2005;11:7901-7910.
Kuss I, Hathaway B, Ferris RL, Gooding W, Whiteside TL. Decreased absolute counts of T lymphocyte
subsets and their relation to disease in squamous cell carcinoma of the head and neck. Clin Can Res
2004;10:3755-3762.
Kuss I, Schaefer C, Godfrey TE, Ferris RL, Harris JM, Gooding W, Whiteside TL. Recent thymic
emigrants and subsets of naive and memory T cells in the circulation of patients with head and neck
cancer. Clin Immunol 2005;116:27-36.
Lopez-Albaitero A, Nayak JV, Ogino T, Machandia A, Gooding W, DeLeo AB, Ferrone S, Ferris RL.
Role of antigen-processing machinery in the in vitro resistance of squamous cell carcinoma of the head and
neck cells to recognition by CTL. J Immunol 2006;176:3402-3409.
Sirianni NM, Ha PK, Oelke M, Califano J, Gooding W, Westra W, Whiteside TL, Koch WM, Schneck
JP, DeLeo A, Ferris RL. Effect of human papillomavirus-16 infection on CD8+ T cell recognition of a wild
type sequence p53264-272 peptide in head and neck cancer patients. Clin Can Res 2004;10:6929-6937.
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