Intra-tumoral hypoxia promotes CD8+ T cell dysfunction via chronic activation of integrated stress response transcription factor ATF4
Coral del Mar Alicea Pauneto, Brian Riesenberg, Evelyn J. Gandy, Andrew S. Kennedy, Genevieve Clutton, Jessica Hem, Katie E. Hurst, Elizabeth G. Hunt, Jarred M Green, Brian C. Miller, Steven P. Angus, Gary L. Johnson, Robert J. Esther, Jennifer L. Guerriero, Peng Gao, David R. Soto‐Pantoja, Robert L. Ferris, Jennifer L. Modliszewski, Michael F. Coleman, H. Kay Chung, J. Justin Milner, Stergios J. Moschos, R. Luke Wiseman, Jessica E. Thaxton
Abstract
TILs as a barrier to ICI response, positioning ISR therapeutics as candidates for immunotherapy.
Topics & Concepts
ATF4Integrated stress responseTranscription factorBiologyCancer researchTumor microenvironmentOxidative stressT cellHypoxia (environmental)Immune systemProgrammed cell deathCell biologyCellMitochondrionUnfolded protein responseImmunologyCell growthApoptosisChronic stressTranscription (linguistics)Signal transductionHypoxia-inducible factorsReceptorImmune checkpointCell cultureReactive oxygen speciesSTAT3Immune Cell Function and InteractionEndoplasmic Reticulum Stress and DiseaseAdipose Tissue and Metabolism