Abstracts for the 25th Annual Scientific Meeting of the International ...

J Immunother Volume 33, Number 8, October 2010
Abstracts
Blockade of CXCL8/IL-8 and CXCL10/IP-10 resulted in dramatic
and moderate inhibition of NK cell migration, respectively.
Additionally, recombinant CXCL8/IL-8 induced specific chemotaxis
of CD56lo CD16+, while CXCL10/IP-10 attracted primarily
CD56hi CD16- NK cells. Overall, these data show that Ad.DC
effectively recruit both major subsets of NK cells, which, coupled
with their ability to activate NK cells, makes them potent immune
activators of not only adaptive, but also innate immune responses.
The study also newly defines CXCL8/IL-8 as one of the crucial
mechanisms by which DC recruit NK cells.
Functional Reconstitution of NKT Cells in Cancer and
Chronic Viral Diseases
Prakash Thapa*, Pramod Nehetew, Hong Hez, Bharti Nehetey,
Stephanie BuchlJ, Lara M. Bully, Jianfei QianJ, Qing YiJ,
Hongzhou Luz, Haoxiang Zhu#, Jiming Zhang#, Peng G.
Wang**, Roberto C. Arduinoww, Jagan Sastrywzzz, Dapeng
Zhou*zz. *Melanoma Medical Oncology; w Veterinary Sciences;
zImmunology; JLymphoma and Myeloma, University of Texas MD
Anderson Cancer Center; yClinical Epidemiology and Outcomes
Division, Baylor College of Medicine; wwSection of Infectious
Diseases, University of Texas Health Science Center at Houston
School of Medicine; zzGraduate School of Biological Sciences,
University of Texas Health Science Center at Houston, Houston,
TX; zShanghai Public Health Clinical Center; #Laboratory of Viral
Hepatitis, Huashan Hospital, Shanghai Medical Collge, Shanghai,
China; **Chemistry and Biochemistry, Ohio State Univeristy,
Columbus, OH.
Natural killer T cells are an innate type of immune cells responsible
for first line of anti-cancer and anti-viral defense, through crosstalk
with downstream antigen presenting cells, NK cells, and adaptive
immune cells. Previous studies indicate that activation of NKT cells
in mouse models of human diseases may elicit tumor or virusspecific
adaptive immune responses. Alpha-galactosylceramide, a
marine sponge-derived agonist ligand for NKT cells, has been
evaluated for its efficacy in treating cancer and hepatitis in several
clinical trials. In this study, we evaluated the effect of repeated
treatment with alpha-galactosylceramide-loaded dendritic cells
(aGalCer/DC) on adaptive immunity, in rhesus monkeys infected
with SHIV. We found that NKT cells could be expanded in vivo,
and were capable of producing anti-viral cytokines. Downstream
activation of SHIV-specific CD8 T cells was observed in 4 out of 7
SHIV-infected rhesus monkeys treated with aGalCer/DC. aGal-
Cer/DC treatment was safe, and did not cause viral replication in
infected monkeys. Although previous studies suggested that the
function of NKT cells is severely impaired in HIV-1 infected
human individuals, we found that NKT cells could be expanded
from HIV-1 patients with low and medium viral load, but not from
advanced AIDS patients. Our results indicate that NKT cells in
cancer and chronic viral infections are interesting targets for
therapeutic intervention. Activation of NKT cells may induce anticancer
and anti-viral cytokine release and activation of adaptive
immune cells. Our data also encourage development of NKT
activating pharmaceuticals targeted at dendritic cells, such as alphagalactosylceramide
conjugated to biodegradable nanoparticles.
In Vivo 6-thioguanine-resistant T Cells from Melanoma
Patients Contain T Cells with Melanoma Specificity as well
as T Cells with Suppressive Function
Cindy L. Zuleger*, Michael D. Macklin*, Michael A. Newton*w,
Mark R. Albertini*zy. *University of Wisconsin Carbone Comprehensive
Cancer Center, University of Wisconsin School of Medicine
and Public Health; w Statistics; zMedicine, University of Wisconsin
School of Medicine and Public Health; yWilliam S. Middleton
Memorial Veteran’s Hopital, Madison, WI.
In vivo hypoxanthine-guanine phosphoribosyltransferase (HPRT)-
deficient T cells (MT) from melanoma patients are enriched for
T cells with in vivo clonal amplifications and can traffic between
blood and tumor tissues. The purpose of this study was to
determine if in vivo MT from metastatic melanoma patients
contained T cells with melanoma specificity as well as T cells with
suppressive function (Tregs). MT were obtained by 6-thioguanine
(TG) selection of lymphocytes from peripheral blood and from
sites of melanoma tumor, and wild-type T cells (WT) were obtained
analogously without TG selection. Using a pool of 5 peptide-MHC
Class I pentamers for melanoma-associated antigens, a significant
enrichment of melanoma-specific T cells in MT compared to WT
was demonstrated in 3 of 5 tumor mass cultures (P