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ICAM-1 Contributes to but Is Not Essential for Tumor Antigen Cross-Priming and CD8⁺ T Cell-Mediated Tumor Rejection In Vivo¹

Christian Blank^2,*,, Ian Brown^*, Aalok K. Kacha^*, Mary A. Markiewicz^* and Thomas F. Gajewski^3,*

Departments of ^* Pathology and Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL 60637

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 TCR^–/– vs ICAM^–/–/TCR^–/– recipient animals. ICAM-1-deficient mice successfully rejected HTR.C tumors expressing L^d 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 K^b, which is cross-presented by APCs in H-2^b mice in vivo. These tumors also grew more slowly but were eventually rejected by the majority of ICAM-1^–/–/TCR^–/– 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.

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