ICAM-1 contributes to but is not essential for tumor antigen cross-priming and CD8+ T cell-mediated tumor rejection in vivo

Christian Blank, Ian Elliott Brown, Aalok K. Kacha, Mary A. Markiewicz, Thomas F. Gajewski

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

ICAM-1 has been described to provide both adhesion and costimulatory functions during T cell activation. In the setting of antitumor immunity, ICAM-1/LFA-1 interactions could be important at the level of T cell priming by APCs in draining lymph nodes as well as for transendothelial migration and tumor cell recognition at the tumor site. To determine the contribution of ICAM-1 to tumor rejection in vivo, we performed adoptive transfer of 2C TCR-transgenic/RAG2-/- T cells into TCRα-/- vs ICAM-/-/TCRα-/- recipient animals. ICAM-1-deficient mice successfully rejected HTR.C tumors expressing Ld recognized by the 2C TCR, albeit with a kinetic delay. Inasmuch as HTR.C tumor cells themselves express ICAM-1, a second model was pursued using B16-F10 melanoma cells that lack ICAM-1 expression. These cells were transduced to express the SIYRYYGL peptide recognized by the 2C TCR in the context of Kb, which is cross-presented by APCs in H-2b mice in vivo. These tumors also grew more slowly but were eventually rejected by the majority of ICAM-1 -/-/TCRα-/- recipients. Delayed rejection in ICAM-1-/- mice was associated with diminished T cell priming as assessed by ELISPOT. In contrast, T cell penetration into the tumor was comparable in wild-type and ICAM-1-/- hosts, and adoptively transferred primed effector 2C cells rejected normally in ICAM-1-/- recipients. Our results suggest that ICAM-1 contributes to but is not absolutely required for CD8+ T cell-mediated tumor rejection in vivo and dominantly acts at the level of priming rather than the effector phase of the antitumor immune response.

Original languageEnglish (US)
Pages (from-to)3416-3420
Number of pages5
JournalJournal of Immunology
Volume174
Issue number6
StatePublished - Mar 15 2005
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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