| Autor: |
Luis-Alberto Perez-Quintero, Zuzet Martinez-Cordoba, Cedric Carli, Alexandre Poirier, Samaneh Kamyabiazar, Chu-Han Feng, Alain Pacis, Yevgen Zolotarov, Kelly-Anne Pike, Jean-Sebastien Delisle, Michel L. Tremblay |
| Rok vydání: |
2023 |
| DOI: |
10.1101/2023.04.17.537264 |
| Popis: |
Activation of cytolytic responses is proven fundamental for the control of tumoral cells. Increased understanding of the modulatory pathways controlling CD8 T cells had led to the formulation of successful checkpoint inhibitor-based immunotherapies against cancer. However, superfluous mechanisms acting to prevent immunopathology can further restrict immune activation. PTPN1 and PTPN2 are two homologous tyrosine phosphatases halting alternative CD8 activating pathways such as the proinflammatory cytokines and the TCR conferring them exceptional immunotherapeutic potential. Herein we investigated to what extent their homology translates into functional redundancy in CD8 T cells, exploring the potential benefits or risks of inhibiting them synchronously. Our results demonstrated that hemizygous deletion of PTPN1 in a PTPN2 deficient background heightens the enhanced effector phenotype already observed in PTPN2 defective CD8 T cells. This effect was evident in their transcriptomic signature and was reproducible with small- molecule inhibitors simultaneously hindering both phosphatases. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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