Progression of Lung Cancer is Associated with Increased Dysfunction of T Cells Defined by Coexpression of Multiple Inhibitory Receptors

Thommen, Daniela Stefanie and Schreiner, Jens and Müller, Philipp and Herzig, Petra and Roller, Andreas and Belousov, Anton and Umana, Pablo and Pisa, Pavel and Klein, Christian G. and Bacac, Marina and Fischer, Ozana S. and Moersig, Wolfgang and Savic Prince, Spasenija and Levitsky, Victor and Karanikas, Vaios and Lardinois, Didier and Zippelius, Alfred. (2015) Progression of Lung Cancer is Associated with Increased Dysfunction of T Cells Defined by Coexpression of Multiple Inhibitory Receptors. Cancer Immunology Research, 3 (12). pp. 1344-1355.

Full text not available from this repository.

Official URL: http://edoc.unibas.ch/43259/

Downloads: Statistics Overview


Dysfunctional T cells present in malignant lesions are characterized by a sustained and highly diverse expression of inhibitory receptors, also referred to as immune checkpoints. Yet, their relative functional significance in different cancer types remains incompletely understood. In this study, we provide a comprehensive characterization of the diversity and expression patterns of inhibitory receptors on tumor-infiltrating T cells from patients with non-small cell lung cancer. In spite of the large heterogeneity observed in the amount of PD-1, Tim-3, CTLA-4, LAG-3, and BTLA expressed on intratumoral CD8(+) T cells from 32 patients, a clear correlation was established between increased expression of these inhibitory coreceptors and progression of the disease. Notably, the latter was accompanied by a progressively impaired capacity of T cells to respond to polyclonal activation. Coexpression of several inhibitory receptors was gradually acquired, with early PD-1 and late LAG-3/BTLA expression. PD-1 blockade was able to restore T-cell function only in a subset of patients. A high percentage of PD-1(hi) T cells was correlated with poor restoration of T-cell function upon PD-1 blockade. Of note, PD-1(hi) expression marked a particularly dysfunctional T-cell subset characterized by coexpression of multiple inhibitory receptors and thus may assist in identifying patients likely to respond to inhibitory receptor-specific antibodies. Overall, these data may provide a framework for future personalized T-cell-based therapies aiming at restoration of tumor-infiltrating lymphocyte effector functions.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Onkologie > Translationale Onkologie (Zippelius)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Onkologie > Translationale Onkologie (Zippelius)
UniBasel Contributors:Thommen, Daniela
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Association for Cancer Research (AACR)
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:06 Dec 2016 09:31
Deposited On:06 Dec 2016 09:31

Repository Staff Only: item control page