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J Immunol. 2015 Apr 1;194(7):3475-86. doi: 10.4049/jimmunol.1402711. Epub 2015 Feb 27.

CD8+CD103+ tumor-infiltrating lymphocytes are tumor-specific tissue-resident memory T cells and a prognostic factor for survival in lung cancer patients.

Author information

1
INSERM Unité 1186, 94805 Villejuif, France; Institut de Cancérologie Gustave Roussy, 94805 Villejuif, France; Université Paris-Sud, 91400 Orsay, France;
2
Institut de Cancérologie Gustave Roussy, 94805 Villejuif, France; Université Paris-Sud, 91400 Orsay, France; INSERM Unité 981, Institut de Cancérologie Gustave Roussy, 94805 Villejuif, France;
3
Institut de Cancérologie Gustave Roussy, 94805 Villejuif, France; Université Paris-Sud, 91400 Orsay, France; Institut de Cancérologie Gustave Roussy, Plateforme de Bioinformatique, 94805 Villejuif, France;
4
INSERM Unité 1186, 94805 Villejuif, France; Centre Chirurgical Marie-Lannelongue, Service d'Anatomie Pathologique, 92350 Le-Plessis-Robinson, France;
5
Institut Mutualiste Montsouris, Service d'Anatomie Pathologique, 75014 Paris, France; and.
6
Institut de Cancérologie Gustave Roussy, 94805 Villejuif, France; Université Paris-Sud, 91400 Orsay, France; Département de Médecine, Institut de Cancérologie Gustave Roussy, 95805 Villejuif, France.
7
INSERM Unité 1186, 94805 Villejuif, France; Institut de Cancérologie Gustave Roussy, 94805 Villejuif, France; Université Paris-Sud, 91400 Orsay, France; fathia.mami-chouaib@gustaveroussy.fr.

Abstract

We had previously demonstrated the role of CD103 integrin on lung tumor-infiltrating lymphocyte (TIL) clones in promoting specific TCR-mediated epithelial tumor cell cytotoxicity. However, the contribution of CD103 on intratumoral T cell distribution and functions and the prognosis significance of TIL subpopulations in non-small cell lung carcinoma (NSCLC) have thus far not been systematically addressed. In this study, we show that an enhanced CD103(+) TIL subset correlates with improved early stage NSCLC patient survival and increased intraepithelial lymphocyte infiltration. Moreover, our results indicate that CD8(+)CD103(+) TIL, freshly isolated from NSCLC specimens, display transcriptomic and phenotypic signatures characteristic of tissue-resident memory T cells and frequently express PD-1 and Tim-3 checkpoint receptors. This TIL subset also displays increased activation-induced cell death and mediates specific cytolytic activity toward autologous tumor cells upon blockade of the PD-1-PD-L1 interaction. These findings emphasize the role of CD8(+)CD103(+) tissue-resident memory T cells in promoting intratumoral CTL responses and support the rationale for using anti-PD-1 blocking Ab to reverse tumor-induced T cell exhaustion in NSCLC patients.

PMID:
25725111
DOI:
10.4049/jimmunol.1402711
[Indexed for MEDLINE]
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