These metabolic changes are associated with altered mitochondrial morphology and signaling downstream of IL-15 ( 12). Inhibition of mTOR during immunization can skew a larger fraction of cells toward a memory phenotype ( 11). Memory cells undergo metabolic changes distinct from short-lived effector cells, relying on oxidative phosphorylation rather than glycolysis ( 9, 10). Factors associated with augmented memory include lower affinity, lower abundance, or temporally interrupted contacts between the T cell receptor (TCR) and peptide-MHC complexes ( 7, 8). In total, memory cells represent 2–5% of the T cell response given their lower rates of proliferation compared to effector cells( 6). ![]() ![]() Memory T cell subtypes include tissue-resident memory cells that seed the tissues and become sentinel cells for subsequent infections, as well as central and peripheral memory cells that patrol blood, lymph, and secondary lymphoid organs. The majority of CD8 T cells become effector cells, although a few become memory cells. No therapies are specifically designed to improve memory formation in cancer patients.ĬD8 T cell fate decisions occur soon after naive T cells first encounter peptide-MHC on activated dendritic cells ( 5). Anti-CTLA4 may influence both effector and memory responses, although the mechanism by which memory cells form in the context of checkpoint blockade is unclear ( 3, 4). Effector CD8 T cells, including those re-invigorated by checkpoint blockade, can lyse tumor cells and produce cytokines like IFNγ to control tumor growth however, these are not the same cells that confer long-term memory ( 2). Yet, the question of how memory CD8 T cells form in cancer patients is not well understood. So-called “tail of the curve” 5-year survivors are touted as the most significant benefit of immunotherapeutics and rely on memory CD8 T cells to provide long-term immune surveillance ( 1). ![]() Cancer immunotherapy has made remarkable progress, with its signature achievement being extension of overall survival and long-term durable remissions in a minority of patients.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |