Concomitant Tumor Immunity to a Poorly Immunogenic Melanoma Is Prevented by Regulatory T Cells

By M. Turk, J. Guevara-Patiño, G. Rizzuto, M. Engelhorn, A. Houghton. Journal of Experimental Medicine, 2004

595 citations recorded by the source corpus.

Concomitant tumor immunity describes immune responses in a host with a progressive tumor that rejects the same tumor at a remote site. In this work, concomitant tumor immunity was investigated in mice bearing poorly immunogenic B16 melanoma. Progression of B16 tumors did not spontaneously elicit concomitant immunity. However, depletion of CD4+ T cells in tumor-bearing mice resulted in CD8+ T cell–mediated rejection of challenge tumors given on day 6. Concomitant immunity was also elicited by treatment with cyclophosphamide or DTA-1 monoclonal antibody against the glucocorticoid-induced tumor necrosis factor receptor. Immunity elicited by B16 melanoma cross-reacted with a distinct syngeneic melanoma, but not with nonmelanoma tumors. Furthermore, CD8+ T cells from mice with concomitant immunity specifically responded to major histocompatibility complex class I–restricted epitopes of two melanocyte differentiation antigens. RAG1 −/− mice adoptively transferred with CD8+ and CD4+ T cells lacking the CD4+CD25+ compartment mounted robust concomitant immunity, which was suppressed by readdition of CD4+CD25+ cells. Naturally occurring CD4+CD25+ T cells efficiently suppressed concomitant immunity mediated by previously activated CD8+ T cells, demonstrating that precursor regulatory T cells in naive hosts give rise to effective suppressors. These results show that regulatory T cells are the major regulators of concomitant tumor immunity against this weakly immunogenic tumor.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/7921622f36c66b5a96ea3b0622eb815c5ab545e3

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Citations in the corpus

Increased populations of regulatory T cells in peripheral blood of patients with hepatocellular carcinoma. (2005, background): “In another study, depletion of regulatory T cells resulted in a slower growth of B16 melanoma (16, 17).”
Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumor immunity (2005, background): “As eradication of tumors, including B16 tumors, is thought to be inhibited by T regulatory (T reg ) cell”
Regulatory T cells in tumor immunity (2010, background): “which the tumor-bearing host reject an inoculum of the same tumor cells at a distant site, depletion of CD25þCD4þTregs in B16-bearing mice resulted in CD8þ T-cell-mediated rejection of secondary challenged B16 tumors.(48) This indicates that concomitant immunity is controlled by CD25þCD4þTregs.”
Tumor cells convert immature myeloid dendritic cells into TGF-β–secreting cells inducing CD4+CD25+ regulatory T cell proliferation (2005, background): “We investigated the cellular and molecular requirements for T reg cell proliferation during tumor progression in rats bearing colon tumors (18) and in mice with melanoma (19).”
Localized oncolytic virotherapy overcomes systemic tumor resistance to immune checkpoint blockade immunotherapy (2014, methodology): “For our studies, we chose a bilateral flank melanoma model with staggered implantation of tumors at a schedule that was previously demonstrated not to be affected by concomitant immunity (28).”
Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance. (2007, background): “For example, adoptively transferred Treg cells can inhibit tumor-specific CD8 T cell-mediated immunity (Antony et al., 2005; Turk et al., 2004).”
Interleukin-35-mediated induction of a novel regulatory T cell population (2010, background): “T reg cells can prevent antitumor CD8 + T cell responses against the poorly immunogenic B16 melanom”
Immunosuppressive strategies that are mediated by tumor cells. (2007, background): “Supporting these findings, Turk and colleagues demonstrated that selective depletion of Tregs in tumor-bearing mice results in CD8+ T-cellmediated tumor rejection and concomitant immunity to a poorly immunogenic tumor (120).”
Regulatory T cells in cancer. (2006, background): “These findings clearly suggest that Treg cells are major regulators of concomitant tumor immunity.(36) Further evidence for the interference of Treg cells with CD8 T cell-mediated anti-tumor immune responses in vivo was established in a transgenic murine colon carcinoma model where Treg cells abroga”
Immunosuppressive networks in the tumour environment and their therapeutic relevance (2005, background): “The study clearly demonstrates that CD4 + T Reg cells are the major regulators of concomitant tumour immunity against this weakly immunogenic tumou”