Escape from immune surveillance does not result in tolerance to tumor-associated antigens

Fraia Melchionda, Melissa K. McKirdy, Filomena Medeiros, Terry J. Fry, Crystal L. Mackall

Research output: Contribution to journalArticle

Abstract

Despite expression of tumor-associated or tumor-specific antigens by most tumors, evasion of protective T-cell immunity is the rule rather than the exception. Understanding whether tumor immune escape primarily represents T-cell neglect, anergy/tolerance, or quantitative limits of an existent immune response is central to developing new strategies to enhance antitumor immunity. The authors studied the immune response to MB49, a tumor that naturally expresses HY. Immune surveillance was effective following low-dose tumor inocula, since normal female mice showed a diminished incidence and slower growth rate of MB49 compared with T-cell-depleted female mice and male mice. Following high-dose tumor inoculation, females developed large, progressive tumors but continued to demonstrate immune responses to class I and class II restricted HY epitopes. The HY reactive T cells remained capable of executing HY immune responses since T cells adoptively transferred from MB49-bearing animals mediated accelerated HY skin graft rejection compared with those taken from naive mice. Thus, MB49 does not induce immune tolerance to HY but rather escapes immune surveillance largely due to quantitative limits of the immune response. Treatment of tumor-bearing animals with rhIL7 significantly increased the number of T cells responding to HY but did not alter tumor growth rate. These results demonstrate that escape from immune surveillance does not necessarily imply immune tolerance to tumor antigens and that immunotherapy need not overcome tumor-induced tolerance per se, and suggest that substantial opportunities remain in tumor-bearing hosts to amplify weak but persistent antitumor immune responses.

Original languageEnglish (US)
Pages (from-to)329-338
Number of pages10
JournalJournal of Immunotherapy
Volume27
Issue number5
StatePublished - Sep 2004
Externally publishedYes

Fingerprint

Neoplasm Antigens
Neoplasms
T-Lymphocytes
Immune Tolerance
Immunity
Tumor Escape
Graft Rejection
Growth
Immunotherapy
Epitopes
Skin
Incidence

Keywords

  • Antigens/peptides/epitopes
  • Rodent
  • T lymphocytes
  • Tolerance/suppression/anergy
  • Tumor immunity

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

Cite this

Melchionda, F., McKirdy, M. K., Medeiros, F., Fry, T. J., & Mackall, C. L. (2004). Escape from immune surveillance does not result in tolerance to tumor-associated antigens. Journal of Immunotherapy, 27(5), 329-338.

Escape from immune surveillance does not result in tolerance to tumor-associated antigens. / Melchionda, Fraia; McKirdy, Melissa K.; Medeiros, Filomena; Fry, Terry J.; Mackall, Crystal L.

In: Journal of Immunotherapy, Vol. 27, No. 5, 09.2004, p. 329-338.

Research output: Contribution to journalArticle

Melchionda, F, McKirdy, MK, Medeiros, F, Fry, TJ & Mackall, CL 2004, 'Escape from immune surveillance does not result in tolerance to tumor-associated antigens', Journal of Immunotherapy, vol. 27, no. 5, pp. 329-338.
Melchionda F, McKirdy MK, Medeiros F, Fry TJ, Mackall CL. Escape from immune surveillance does not result in tolerance to tumor-associated antigens. Journal of Immunotherapy. 2004 Sep;27(5):329-338.
Melchionda, Fraia ; McKirdy, Melissa K. ; Medeiros, Filomena ; Fry, Terry J. ; Mackall, Crystal L. / Escape from immune surveillance does not result in tolerance to tumor-associated antigens. In: Journal of Immunotherapy. 2004 ; Vol. 27, No. 5. pp. 329-338.
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