Characterizing tumor-promoting T cells in chemically induced cutaneous carcinogenesis.

نویسندگان

  • Scott J Roberts
  • Bernice Y Ng
  • Renata B Filler
  • Julia Lewis
  • Earl J Glusac
  • Adrian C Hayday
  • Robert E Tigelaar
  • Michael Girardi
چکیده

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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Tumor-promoting role of TGFβ1 signaling in ultraviolet B-induced skin carcinogenesis is associated with cutaneous inflammation and lymph node migration of dermal dendritic cells.

Transforming growth factor beta 1 (TGFβ1) is a pleiotropic cytokine in the skin that can function both as a tumor promoter and suppressor in chemically induced skin carcinogenesis, but the function in ultraviolet B (UVB) carcinogenesis is not well understood. Treatment of SKH1 hairless mice with the activin-like kinase 5 (ALK5) inhibitor SB431542 to block UVB-induced activation of cutaneous TGF...

متن کامل

Studying humane endpoints in a rat model of mammary carcinogenesis

Objective(s): The present work intended to clearly define the most adequate humane endpoints in an experimental assay of mammary carcinogenesis in rats. Materials and Methods: Animals were observed twice a day; all parameters were registered once a week and the euthanasia endpoints were established in order to monitor the animal welfare/...

متن کامل

EFFECT OF IRON OVERLOAD ON 7, 12-DIMETHYLBENZ (A) ANTHRACENE-INDUCED SKIN TUMORIGENESIS

Iron overload is known to occur in the West European and American population due to the consumption of iron-rich diets. On the other hand, genetic disorders leading to iron overload are also known. Iron overload leads to increased peroxidation and disruptive disintegration of lipid-rich membranes, and predisposes humans for an enhanced risk of cancer induction. In experimental animals iron ...

متن کامل

Loss of cutaneous TSLP-dependent immune responses skews the balance of inflammation from tumor protective to tumor promoting.

Inflammation can promote or inhibit cancer progression. In this study we have addressed the role of the proinflammatory cytokine thymic stromal lymphopoietin (TSLP) during skin carcinogenesis. Using conditional loss- and gain-of-function mouse models for Notch and Wnt signaling, respectively, we demonstrate that TSLP-mediated inflammation protects against cutaneous carcinogenesis by acting dire...

متن کامل

The atypical chemokine receptor D6 suppresses the development of chemically induced skin tumors.

A subset of CC chemokines, acting through CC chemokine receptors (CCRs) 1 to 5, is instrumental in shaping inflammatory responses. Recently, we and others have demonstrated that the atypical chemokine receptor D6 actively sequesters and destroys many of these proinflammatory CC chemokines. This is critical for effective resolution of inflammation in vivo. Inflammation can be protumorigenic, and...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Proceedings of the National Academy of Sciences of the United States of America

دوره 104 16  شماره 

صفحات  -

تاریخ انتشار 2007