Characterizing tumor-promoting T cells in chemically induced cutaneous carcinogenesis.
There is a longstanding but poorly understood epidemiologic link between inflammation and cancer. Consistent with this, we previously showed that alphabeta T cell deficiency can increase resistance to chemical carcinogenesis initiated by 7,12-dimethylbenz[a]anthracene and promoted by phorbol 12-myristate 13-acetate. This provoked the hypothesis that alphabeta T cell deficiency removed T regulatory cells that limit the anti-tumor response or removed a specific tumor-promoting (T-pro) T cell population. Here we provide evidence for the latter, identifying a novel CD8(+) subset that is a candidate for T-pro cells. We demonstrate that CD8 cell-deficient mice show substantially less tumor incidence and progression to carcinoma, whereas susceptibility is restored by CD8(+) cell reconstitution. To characterize the putative T-pro cells, tumor-infiltrating lymphocytes were isolated from normal and CD4(-/-) mice, revealing an activated population of T cell receptor alphabeta(+)CD8(+)CD44(+)CD62L(-) cells expressing the inflammatory mediators IFNgamma, TNFalpha, and cyclooxygenase-2, but deficient in perforin, relative to recirculating cells of equivalent phenotype. This novel population of CD8(+) T cells has intriguing similarities with other lymphocytes that have been associated with tissue growth and invasiveness and has implications for inflammation-associated carcinogenesis, models of cancer immunosurveillance, and immunotherapeutic strategies.
Roberts
Scott J
SJ
Department of Dermatology, Yale University School of Medicine, New Haven, CT 06520-8059, USA.
Ng
Bernice Y
BY
Filler
Renata B
RB
Lewis
Julia
J
Glusac
Earl J
EJ
Hayday
Adrian C
AC
Tigelaar
Robert E
RE
Girardi
Michael
M
D000818:Animals; D000831:Animals, Newborn; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016130:Immunophenotyping; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology*; D016176:T-Lymphocyte Subsets / Q000378:metabolism / Q000473:pathology* / Q000637:transplantation
D016693:Receptors, Antigen, T-Cell, alpha-beta