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In Situ Sensory Adaptation of Tumor-Infiltrating T Lymphocytes to Peptide-MHC Levels Elicits Strong Antitumor Reactivity¹

Guillaume Dorothée^2,*, Isabelle Vergnon^2,*, Faten El Hage^*, Béatrice Le Maux Chansac^*, Vincent Ferrand, Yann Lécluse, Paule Opolon, Salem Chouaib^*, Georges Bismuth and Fathia Mami-Chouaib^3,*

^* Laboratoire Cytokines et Immunologie des Tumeurs Humaines, Institut National de la Santé et de la Recherche Médicale Unité 487, Institut Fédératif de Recherche 54, and Unité Mixte de Recherche 8126, and Unité Mixte de Recherche 8121, Centre National de la Recherche Scientifique, Institut Gustave Roussy, Villejuif, France; and Institut Cochin, Département de Biologie Cellulaire, Institut National de la Santé et de la Recherche Médicale Unité 567, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104, Université René Descartes, Paris, France

We have isolated from tumor-infiltrating lymphocytes (TIL) and PBL of a lung carcinoma patient several tumor-specific T cell clones displaying similar peptide-MHC tetramer staining and expressing a unique TCR. Although these clones elicited identical functional avidity and similar cytolytic potential, only T cell clones derived from TIL efficiently lysed autologous tumor cells. Interestingly, all of these clones expressed the same T cell surface markers except for the TCR inhibitory molecule CD5, which was expressed at much lower levels in TIL than in PBL. Video-imaging recordings demonstrated that, although both T cell clones could form stable conjugates with tumor cells, the Ca²⁺ response occurred in TIL clones only. Significantly, analysis of a panel of circulating clones indicated that antitumor cytolytic activity was inversely proportional to CD5 expression levels. Importantly, CD5 levels in TIL appeared to parallel the signaling intensity of the TCR/peptide-MHC interaction. Thus, in situ regulation of CD5 expression may be a strategy used by CTL to adapt their sensitivity to intratumoral peptide-MHC levels.

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