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. 1993 Nov;37(6):392–399. doi: 10.1007/BF01526796

Increase in the ability of human cancer cells to induce cytotoxic T lymphocytes by ultraviolet irradiation

Yasuiki Umezu 1, Lazel B Augustus 1, Dai Seito 1, Kazuhiro Hayakawa 1, Merric I Ross 2, Omar Eton 3, David A Swanson 4, Kyogo Itoh 1,5,✉
PMCID: PMC11038243  PMID: 8242664

Abstract

The roles of ultraviolet-B (UV) radiation in the immunogenicity of human cancer cells have not been fully studied. We have investigated the effects of UV radiation on metastatic melanoma and renal cell carcinoma cells with regard to MHC antigen expression and the ability to induce cytotoxic T lymphocyte (CTL) activity in peripheral blood mononuclear cells (PBMC) or tumor-infiltrating lymphocytes (TIL) against untreated autologous tumor cells. UV radiation respectively decreased or increased MHC class I expression of freshly isolated tumor cells or cultured tumor cells, and also decreased MHC class I expression of starved cultured tumor cells. It increased the ability of both freshly isolated and cultured tumor cells to induce CTL activity from PBMC against untreated autologous tumor cells. UV-irradiated subclones that were more susceptible to CTL lysis were more potent for CTL induction from TIL than either an untreated parental clone or a UV-irradiated subclone that was resistant to CTL lysis. In summary, UV radiation increased the ability of tumor cells to induce CTL activity without a corresponding effect on MHC antigen expression.

Key words: Human cancer cells, Immunogenicity, Ultraviolet-B irradiation, Cytotoxic T lymphocytes

Footnotes

This work was supported in part by a grant CA47891 from the National Cancer Institute, USA, a grant-in-aid of the comprehensive 10-years strategy for cancer control from ministry of a Health and Welfare, Japan, and the Ishibashi Research Fund, Japan

References

  • 1.Alexander J, Edinger M, Connelly R, Tubbs R, Pontes E, Bukowski R, Finke J. Isolation of activated CD8+ cells from PBL and tumor-infiltrating lymphocytes (TIL) from renal cell carcinoma (RCC) and their characterization. FASEB J. 1990;4:A2021. [Google Scholar]
  • 2.Alexander J, Rayman P, Edinger M, Connelly R, Tubbs R, Bukowski R, Pontes E, Finke J. TIL from renal cell carcinoma: restimulation with tumor influences proliferation and cytotoxic activity. Int J Cancer. 1990;45:119–124. doi: 10.1002/ijc.2910450121. [DOI] [PubMed] [Google Scholar]
  • 3.Anichini A, Mazzocchi A, Fossati G, Parmiani G. Cytotoxic T lymphocyte clones from peripheral blood and from tumor site detect intratumor heterogeneity of melanoma cells. Analysis of specificity and mechanisms of interaction. J Immunol. 1984;142:3692–3701. [PubMed] [Google Scholar]
  • 4.Applegate LA, Lee RD, Alcalay J, Kripke ML. Identification of the molecular target for the suppression of contact hypersensitivity by ultraviolet radiation. J Exp Med. 1989;170:1117–1131. doi: 10.1084/jem.170.4.1117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Augusts LB, Hayakawa K, von eschenbach AC, Swanson DA, Itoh K. Increase in immunogenicity of human renal cell carcinoma cells by exposure to ultraviolet-B radiation. Proc Amer Assoc Cancer Res. 1992;33:334. [Google Scholar]
  • 6.Balch CM, Riley LB, Bae Y-J, Salmeron MA, Platsoucas CD, von Eschenbach AC, Itoh K. Patterns of human tumor-infiltrating lymphocytes in 120 human cancers. Arch Surg. 1990;125:200–205. doi: 10.1001/archsurg.1990.01410140078012. [DOI] [PubMed] [Google Scholar]
  • 7.Belldegrun A, Muul LM, Rosenberg SA. Interleukin 2 expanded tumor-infiltrating lymphocytes in human renal cell carcinoma: isolation, characterization, and antitumor activity. Cancer Res. 1988;47:206–214. [PubMed] [Google Scholar]
  • 8.Belldegrun A, Kasid A, Uppenkamp M, Topalian SL, Rosenberg SA. Human tumor-infiltrating lymphocytes. Analysis of lymphokine mRNA expression and relevance to cancer immunotherapy. J Immunol. 1989;142:4520–4526. [PubMed] [Google Scholar]
  • 9.Bonmasser VE, Bonmasser A, Vadlamudi S, Goldin A. Immunologic alteration of leukemic cells in vivo after treatment with an antitumor drug. Proc Natl Acad Sci USA. 1970;66:1089–1095. doi: 10.1073/pnas.66.4.1089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Boone C, Blackman K. Augmented immunogenicity of tumor cell homogenates infected with influenza virus. Cancer Res. 1972;32:1018–1022. [PubMed] [Google Scholar]
  • 11.Boon T, Kellerman O. Rejection by syngeneic mice of cell variants obtained by mutagenesis of a malignant teratocarcinoma cell line. Proc Natl Acad Sci USA. 1977;74:272–275. doi: 10.1073/pnas.74.1.272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Carlow DA, Kerbel RS, Feltis JT, Elliott BD. Enhanced expression of class I major histocompatibility complex gene (Dk) products on immunogeneic variants of a spontaneous murine carcinoma. J Natl Cancer Inst. 1985;75:291–300. [PubMed] [Google Scholar]
  • 13.Contessa AR, Bonmasser A, Giampietri A, Circolo A, Goldin A, Fioretti MC. In vitro generation of a highly immunogenic subline of L1210 leukemia following exposure to 5-(3′-dimethyl-triazeno)imidazole-4-carboxamide. Cancer Res. 1981;41:2476–2482. [PubMed] [Google Scholar]
  • 14.Darrow TL, Slingluff CL, Seigler HF. The role of HLA class I antigens in recognition of melanoma cells by tumor-specific cytotoxic T lymphocytes; evidence for shared tumor antigens. J Immunol. 1989;142:3329–3335. [PubMed] [Google Scholar]
  • 15.Daynes RA, Schmitt MK, Roberts LK, Spellman CW. Phenotypic and physical characteristics of the lymphoid cells involved in the immunity to syngeneic UV-induced tumors. J Immunol. 1979;122:2458–2464. [PubMed] [Google Scholar]
  • 16.Fearon ER, Pardoll DM, Itaya T, Golumbek P, Levitsky HI, Simons JW, Karasuyama H, Vogelstein B, Frost P. Interleukin-2 production by tumor cells bypasses T helper function in the generation of an anti-tumor response. Cell. 1990;60:397–402. doi: 10.1016/0092-8674(90)90591-2. [DOI] [PubMed] [Google Scholar]
  • 17.Finke JH, Rayman P, Alexander J, Edinger M, Tubbs RR, Connelly R, Pontes E, Bukowski R. Characterization of the cytotoxic activity of CD4+ and CD8+ tumor-infiltrating lymphocytes in human renal cell carcinoma. Cancer Res. 1990;50:2363–2370. [PubMed] [Google Scholar]
  • 18.Fisher MS. A systemic effect of UV-irradiation and its relationship to tumor immunity. Natl Cancer Inst Monogr. 1978;50:185–188. [PubMed] [Google Scholar]
  • 19.Fishleder AJ, Finke JH, Tubbs R, Bukowski RM. Induction by interleukin-2 of oligoclonal expansion of cultured tumor-infiltrating lymphocytes. J Natl Cancer Inst. 1990;82:124–128. doi: 10.1093/jnci/82.2.124. [DOI] [PubMed] [Google Scholar]
  • 20.Fortner GW, Kripke ML. In vitro reactivity of splenic lymphocytes from normal and UV-irradiated mice against syngeneic UV-induced tumors. J Immunol. 1977;118:1483–1487. [PubMed] [Google Scholar]
  • 21.Frost P, Kerbel RS, Bauer E, Tartamella-Biondo R, Cefalu W. Mutagen treatment as a means for selecting immunogenic variants from otherwise poorly immunogenic malignant murine tumors. Cancer Res. 1983;43:125–132. [PubMed] [Google Scholar]
  • 22.Fuji H, Mihich E. Selection for high immunogenicity in drugresistant sublines of murine lymphomas demonstrated by plaque assay. Cancer Res. 1975;35:946–952. [PubMed] [Google Scholar]
  • 23.Graffi A, Pasternak G, Horn K-H. Die Erzeugung von Resistenz gegen infolge transplantierter UV-induzierter Sarkome der Maus. Acta Biol Med Ger. 1964;12:726–732. [PubMed] [Google Scholar]
  • 24.Hayakawa K, Salmeron MA, Parkinson DR, Markowitz AB, von Eschenbach AC, Legha SS, Balch CM, Ross MI, Augustus LB, Itoh K. Study of tumor-infiltrating lymphocytes for adoptive therapy of renal cell carcinoma (RCC) and metastatic melanoma. Sequential proliferation of cytotoxic natural killer and noncytotoxic T cells in RCC. J Immunother. 1991;10:313–325. doi: 10.1097/00002371-199110000-00003. [DOI] [PubMed] [Google Scholar]
  • 25.Hayakawa K, Morita T, Augustus LB, von Eschenbach AC, Itoh K. Human renal cell carcinoma cells are able to activate natural killer cells. Int J Cancer. 1992;51:290–295. doi: 10.1002/ijc.2910510219. [DOI] [PubMed] [Google Scholar]
  • 26.Hersey P, MacDonald M, Schibeci S, Burns C. Clonal analysis of cytotoxic T lymphocytes (CTL) against autologous melanoma. Cancer Immunol Immunother. 1986;22:15–23. doi: 10.1007/BF00205711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Hostetler LW, Kripke ML. Origin and significance of transplantation antigens induced on cells transformed by UV radiation. In: Greene MI, Hamaoka T, editors. Development and recognition of the transformed cells. New York: Plenum; 1987. pp. 307–329. [Google Scholar]
  • 28.Hostetler LW, Kripke ML. Proportion of antigenic variants indued by in vitro UV irradiation differs in clones derived from a single tumor. J Immunol. 1988;140:666–670. [PubMed] [Google Scholar]
  • 29.Hostetler LW, Ananthaswamy HN, Kripke ML. Generation of tumor-specific transplantation antigens by UV radiation can occur independently of neoplastic transplantation. J Immunol. 1986;137:2721–2725. [PubMed] [Google Scholar]
  • 30.Hui K, Grosveld F, Festenstein H. Rejection of transplantable AKR leukemia cells following MHC DNA-mediated cell transformation. Nature. 1985;311:750–752. doi: 10.1038/311750a0. [DOI] [PubMed] [Google Scholar]
  • 31.Itoh K, Platsoucas CD, Balch CM. Autologous tumor-specific cytotoxic T lymphocytes in the infiltrates of human metastatic melanoma. Activation by interleukin 2 and autologous tumor cells, and involvement of the T cell receptor. J Exp Med. 1988;168:1419–1441. doi: 10.1084/jem.168.4.1419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Kerbel RS. Immunologic studies of membrane mutants of a highly metastatic murine tumor. Am J Pathol. 1979;97:609–622. [PMC free article] [PubMed] [Google Scholar]
  • 33.Kobayashi H, Sendo F, Shirai T, Kaji H, Kodama T. Modification in growth of transplantable rat tumors exposed to friend virus. J Natl Cancer Inst. 1969;42:413–418. [PubMed] [Google Scholar]
  • 34.Kripke ML. Antigenicity of murine skine tumors induced by ultraviolet light. J Natl Cancer Inst. 1974;53:1333–1336. doi: 10.1093/jnci/53.5.1333. [DOI] [PubMed] [Google Scholar]
  • 35.Kripke ML. Latency, histology, and antigenicity of tumors induced by ultraviolet light in three inbred mouse strains. Cancer Res. 1977;37:1395–1399. [PubMed] [Google Scholar]
  • 36.Lindermann J, Klein P. Viral oncolysis: increased immunogenicity of host cell antigen associated with influenza virus. J Exp Med. 1967;126:93–108. doi: 10.1084/jem.126.1.93. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Mansfield PF, Salmeron MA, Rosenblum MG, Itoh K. Effects of HC antibody in autologous tumor-specific cytotoxicity by human melanoma tumor-infiltrating lymphocytes. Int J Cancer. 1991;49:356–361. doi: 10.1002/ijc.2910490307. [DOI] [PubMed] [Google Scholar]
  • 38.Patrick MH, Rahn RO. Photochemistry of DNA and polynucleotides: photoproducts. In: Wang SY, editor. Photochemistry and photobiology of nucleic acid. New York: Academic Press; 1976. pp. 35–95. [Google Scholar]
  • 39.Peppoloni S, Herberman RB, Gorelik E. Induction of highly immunogenic variants of Lewis lung carcinoma by ultraviolet irradiation. Cancer Res. 1985;45:2526–2536. [PubMed] [Google Scholar]
  • 40.Schmid FA, Hutchison DJ. Decrease in oncogenic potential of L1210 leukemia by triazenes. Cancer Res. 1973;33:2161–2165. [PubMed] [Google Scholar]
  • 41.Tepper RI, Pattengale PK, Leder P. Murine interleukin 4 displays potent anti-tumor activity in vivo. Cell. 1989;57:503–512. doi: 10.1016/0092-8674(89)90925-2. [DOI] [PubMed] [Google Scholar]
  • 42.Thorn RT. Specific inhibition of cytotoxic memory cells produced against UV-induced tumors in UV irradiated mice. J Immunol. 1978;121:1920–1926. [PubMed] [Google Scholar]
  • 43.Uyttenhove C, Van Snick J, Boon T. Immunogenic variants obtained by mutagenesis of mouse mastocytoma P815. I. Rejection by syngeneic mice. J Exp Med. 1980;152:1175–1183. doi: 10.1084/jem.152.5.1175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Van Pel A, Vessiere F, Boon T. Protection against two spontaneous mouse leukemias conferred by immunogenic variants obtainead by mutagenesis. J Exp Med. 1983;457:1992–2001. doi: 10.1084/jem.157.6.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.Wallich R, Bulbuc N, Hammerling GJ, Katsav S, Segel S, Feldman M. Abrogation of metastatic properties of tumor cells by de novo expression of H-2 K antigens following H-2 gene transfection. Nature. 1985;315:301–305. doi: 10.1038/315301a0. [DOI] [PubMed] [Google Scholar]
  • 46.Weber JS, Jay G, Tanaka K, Rosenberg RA. Immunotherapy of a murine tumor with interleukin 2. Increased sensitivity after MHC Class I gene transfection. J Exp Med. 1987;166:1716–1733. doi: 10.1084/jem.166.6.1716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Wortzel RD, Urban JL, Schreiber H. Malignant growth in the normal host after variant selection in vitro with cytolytic T-cell lines. Proc Natl Acad Sci USA. 1984;81:2186–2190. doi: 10.1073/pnas.81.7.2186. [DOI] [PMC free article] [PubMed] [Google Scholar]

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