CD8+CD103+ tumor-infiltrating lymphocytes are tumor-specific tissue-resident memory T cells and a prognostic factor for survival in lung cancer patients.
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.
INSERM Unité 1186, 94805 Villejuif, France; Institut de Cancérologie Gustave Roussy, 94805 Villejuif, France; Université Paris-Sud, 91400 Orsay, France;
Fayçal
F
Djenidi
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;
Julien
J
Adam
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;
Aïcha
A
Goubar
INSERM Unité 1186, 94805 Villejuif, France; Institut de Cancérologie Gustave Roussy, 94805 Villejuif, France; Université Paris-Sud, 91400 Orsay, France;
Aurélie
A
Durgeau
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;
Guillaume
G
Meurice
INSERM Unité 1186, 94805 Villejuif, France; Centre Chirurgical Marie-Lannelongue, Service d'Anatomie Pathologique, 92350 Le-Plessis-Robinson, France;
Vincent
V
de Montpréville
Institut Mutualiste Montsouris, Service d'Anatomie Pathologique, 75014 Paris, France; and.
Pierre
P
Validire
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.
Benjamin
B
Besse
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.
Fathia
F
Mami-Chouaib
D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000401:mortality / Q000473:pathology; D003602:Cytotoxicity, Immunologic; D005260:Female; D020869:Gene Expression Profiling; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D039001:Integrin alpha Chains / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology* / Q000401:mortality* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D009928:Organ Specificity / Q000276:immunology; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors
D015703:Antigens, CD; D016827:CD8 Antigens; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D039001:Integrin alpha Chains; D008565:Membrane Proteins; D061026:Programmed Cell Death 1 Receptor; C091367:alpha E integrins