Depletion of CD4+CD25+ regulatory T cells promotes a tumor-specific immune response in pancreas cancer-bearing mice.
BACKGROUND
Pancreas cancer-bearing mice have an increased prevalence of immunosuppressive CD4(+)CD25(+) regulatory T cells (T(reg)). Depletion of T(reg) results in smaller tumors and prolonged host survival. The objective of this study was to evaluate the tumor-specific immune response after depletion of T(reg) alone or in combination with a cancer vaccine.


METHODS
Four groups of C57BL/6 mice were challenged with pancreas adenocarcinoma cells (Pan02). The mice received four combinations of antibody-mediated T(reg) depletion and whole tumor cell vaccination: (1) no treatment, (2) T(reg) depletion only, (3) vaccination only, or (4) T(reg) depletion and vaccination. Splenocytes and lymphocytes from tumor-draining lymph nodes were analyzed for tumor-specific release of interferon gamma by enzyme-linked immunosorbent spot assay.


RESULTS
In T(reg)-depleted and vaccinated mice, a strong statistical trend toward smaller tumors (P = .05) and longer survival (P = .054) was found compared with untreated mice. T(reg)-depleted mice showed significantly more tumor-specific cells than undepleted mice (P = .02). The number of tumor-specific cells was significantly higher in tumor-draining lymph nodes than in the spleen (P = .002). Similarly, significantly more tumor-specific cells were found in spleens of T(reg)-depleted and vaccinated mice than in vaccinated-only mice (P = .009).


CONCLUSIONS
Depletion of T(reg) alone or in combination with a whole tumor cell vaccine promotes a tumor-specific immune response. Thus, strategies incorporating T(reg) depletion might improve the efficacy of cancer vaccines.
Viehl
Carsten T
CT
Department of Surgery, Washington University School of Medicine, Box 8109, 660 S. Euclid Ave., St. Louis, Missouri 63110, USA.
Moore
Todd T
TT
Liyanage
Udaya K
UK
Frey
Daniel M
DM
Ehlers
Jesmin P
JP
Eberlein
Timothy J
TJ
Goedegebuure
Peter S
PS
Linehan
David C
DC
D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D019496:Cancer Vaccines / Q000627:therapeutic use; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D007371:Interferon-gamma / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015375:Receptors, Interleukin-2 / Q000276:immunology / Q000378:metabolism*; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor