The Distinct Contributions of Murine T Cell Receptor (TCR)gammadelta+ and TCRalphabeta+ T Cells to Different Stages of Chemically Induced Skin Cancer

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2003 Sep 4

PMID 12953094

Citations 74

Authors

Michael Girardi

Earl Glusac

Renata B Filler

Scott J Roberts

Iva Propperova

Julia Lewis

Robert E Tigelaar

Adrian C Hayday

Affiliations

Soon will be listed here.

Abstract

Epithelial tissues in which carcinomas develop often contain systemically derived T cell receptor (TCR)alphabeta+ cells and resident intraepithelial lymphocytes that are commonly enriched in TCRgammadelta+ cells. Recent studies have demonstrated that gammadelta cells protect the host against chemically induced cutaneous malignancy, but the role of alphabeta T cells has been enigmatic, with both protective and tumor-enhancing contributions being reported in different systems. This study aims to clarify the contributions of each T cell type to the regulation of squamous cell carcinoma induced in FVB mice by a two-stage regimen of 7,12-dimethylbenz[a]anthracene initiation followed by repetitive application of the tumor promoter 12-O-tetradecanoylphorbol 13-acetate. This protocol permits one to monitor the induction of papillomas and the progression of those papillomas to carcinomas. The results show that whereas gammadelta cells are strongly protective, the nonredundant contributions of alphabeta T cells to the host's protection against papillomas are more modest. Furthermore, at both high and low doses of carcinogens, alphabeta T cells can contribute to rather than inhibit the progression of papillomas to carcinomas. As is likely to be the case in humans, this study also shows that the contribution of T cells to tumor immunosurveillance is regulated by modifier genes.

Citing Articles

Gut Microbiota Regulates the Homeostasis of Dendritic Epidermal T Cells.

Chung J, Lee J, Oh H, Kim Y, Lim S, Lee C Life (Basel). 2025; 14(12.

PMID: 39768401 PMC: 11677426. DOI: 10.3390/life14121695.

Ontogeny and function of the intestinal epithelial and innate immune cells during early development of chicks: to explore in ovo immunomodulatory nutrition.

Ayalew H, Xu C, Adane A, Sanchez A, Li S, Wang J Poult Sci. 2024; 104(1):104607.

PMID: 39693955 PMC: 11720616. DOI: 10.1016/j.psj.2024.104607.

Emerging Innate Immune Cells in Cancer Immunotherapy: Promises and Challenges.

Wu J BioDrugs. 2024; 38(4):499-509.

PMID: 38700835 PMC: 11246812. DOI: 10.1007/s40259-024-00657-2.

TCR-Vγδ usage distinguishes protumor from antitumor intestinal γδ T cell subsets.

Reis B, Darcy P, Khan I, Moon C, Kornberg A, Schneider V Science. 2022; 377(6603):276-284.

PMID: 35857588 PMC: 9326786. DOI: 10.1126/science.abj8695.

Lrig1- and Wnt-dependent niches dictate segregation of resident immune cells and melanocytes in murine tail epidermis.

Baess S, Burkhart A, Cappello S, Graband A, Sere K, Zenke M Development. 2022; 149(14).

PMID: 35815643 PMC: 9382897. DOI: 10.1242/dev.200154.

References

Siegel C, Schreiber K, Meredith S, Lancki D, Lazarski C, Fu Y . Enhanced growth of primary tumors in cancer-prone mice after immunization against the mutant region of an inherited oncoprotein. J Exp Med. 2000; 191(11):1945-56. PMC: 2213520. DOI: 10.1084/jem.191.11.1945. View

Pentland A, Schoggins J, Scott G, Khan K, Han R . Reduction of UV-induced skin tumors in hairless mice by selective COX-2 inhibition. Carcinogenesis. 1999; 20(10):1939-44. DOI: 10.1093/carcin/20.10.1939. View

Holtmeier W, Pfander M, Hennemann A, Zollner T, Kaufmann R, Caspary W . The TCR-delta repertoire in normal human skin is restricted and distinct from the TCR-delta repertoire in the peripheral blood. J Invest Dermatol. 2001; 116(2):275-80. DOI: 10.1046/j.1523-1747.2001.01250.x. View

Peto J . Cancer epidemiology in the last century and the next decade. Nature. 2001; 411(6835):390-5. DOI: 10.1038/35077256. View

Banchereau J, Palucka A, Dhodapkar M, Burkeholder S, Taquet N, Rolland A . Immune and clinical responses in patients with metastatic melanoma to CD34(+) progenitor-derived dendritic cell vaccine. Cancer Res. 2001; 61(17):6451-8. View

Fahrer A, Konigshofer Y, Kerr E, Ghandour G, Mack D, Davis M . Attributes of gammadelta intraepithelial lymphocytes as suggested by their transcriptional profile. Proc Natl Acad Sci U S A. 2001; 98(18):10261-6. PMC: 56949. DOI: 10.1073/pnas.171320798. View

Shires J, Theodoridis E, Hayday A . Biological insights into TCRgammadelta+ and TCRalphabeta+ intraepithelial lymphocytes provided by serial analysis of gene expression (SAGE). Immunity. 2001; 15(3):419-34. DOI: 10.1016/s1074-7613(01)00192-3. View

Girardi M, Oppenheim D, Steele C, Lewis J, Glusac E, Filler R . Regulation of cutaneous malignancy by gammadelta T cells. Science. 2001; 294(5542):605-9. DOI: 10.1126/science.1063916. View

Hayday A, Theodoridis E, Ramsburg E, Shires J . Intraepithelial lymphocytes: exploring the Third Way in immunology. Nat Immunol. 2001; 2(11):997-1003. DOI: 10.1038/ni1101-997. View

10.

Girardi M, Lewis J, Glusac E, Filler R, Geng L, Hayday A . Resident skin-specific gammadelta T cells provide local, nonredundant regulation of cutaneous inflammation. J Exp Med. 2002; 195(7):855-67. PMC: 2193718. DOI: 10.1084/jem.20012000. View

11.

Orengo I, Gerguis J, Phillips R, Guevara A, Lewis A, Black H . Celecoxib, a cyclooxygenase 2 inhibitor as a potential chemopreventive to UV-induced skin cancer: a study in the hairless mouse model. Arch Dermatol. 2002; 138(6):751-5. DOI: 10.1001/archderm.138.6.751. View

12.

Daniel D, Meyer-Morse N, Bergsland E, Dehne K, Coussens L, Hanahan D . Immune enhancement of skin carcinogenesis by CD4+ T cells. J Exp Med. 2003; 197(8):1017-28. PMC: 2193878. DOI: 10.1084/jem.20021047. View

13.

Ferguson A . Intraepithelial lymphocytes of the small intestine. Gut. 1977; 18(11):921-37. PMC: 1411743. DOI: 10.1136/gut.18.11.921. View

14.

Asarnow D, Kuziel W, Bonyhadi M, Tigelaar R, Tucker P, Allison J . Limited diversity of gamma delta antigen receptor genes of Thy-1+ dendritic epidermal cells. Cell. 1988; 55(5):837-47. DOI: 10.1016/0092-8674(88)90139-0. View

15.

Hennings H, Glick A, Lowry D, Krsmanovic L, Sly L, Yuspa S . FVB/N mice: an inbred strain sensitive to the chemical induction of squamous cell carcinomas in the skin. Carcinogenesis. 1993; 14(11):2353-8. DOI: 10.1093/carcin/14.11.2353. View

16.

Boismenu R, Havran W . Modulation of epithelial cell growth by intraepithelial gamma delta T cells. Science. 1994; 266(5188):1253-5. DOI: 10.1126/science.7973709. View

17.

Williams I, Ort R, Daley D, Manning L, Karaoli T, Barnhill R . Constitutive expression of B7-1 (CD80) on mouse keratinocytes does not prevent development of chemically induced skin papillomas and carcinomas. J Immunol. 1996; 156(9):3382-8. View

18.

Peng S, Robert M, Hayday A, Craft J . A tumor-suppressor function for Fas (CD95) revealed in T cell-deficient mice. J Exp Med. 1996; 184(3):1149-54. PMC: 2192794. DOI: 10.1084/jem.184.3.1149. View

19.

Rosenberg S, Yang J, Schwartzentruber D, Hwu P, Marincola F, Topalian S . Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma. Nat Med. 1998; 4(3):321-7. PMC: 2064864. DOI: 10.1038/nm0398-321. View

20.

Groh V, Rhinehart R, Secrist H, Bauer S, Grabstein K, Spies T . Broad tumor-associated expression and recognition by tumor-derived gamma delta T cells of MICA and MICB. Proc Natl Acad Sci U S A. 1999; 96(12):6879-84. PMC: 22010. DOI: 10.1073/pnas.96.12.6879. View