CD8B encodes the beta subunit of the CD8 coreceptor, an integral membrane glycoprotein essential for adaptive immune responses. CD8B functions as a coreceptor that simultaneously engages T-cell receptors (TCR) and MHC class I molecules on antigen-presenting cells, recruiting the Src kinase LCK to initiate intracellular signaling cascades that activate cytotoxic T-lymphocytes 1. The protein's cytoplasmic tail contains a palmitoylation site enabling lipid raft partitioning, which enriches signaling proteins critical for T-cell activation 1. CD8B plays a pivotal role in thymic selection of CD8+ T-cells during development 1. Clinically, CD8B expression serves as a prognostic biomarker in cancer immunotherapy. CD8B gene expression correlates with CD8+ T-cell tumor infiltration and predicts response to anti-PD-1/PD-L1 immunotherapy across multiple solid tumors 2. High CD8B/FOXP3 and CD8B/ENTPD1 ratios are significantly associated with positive responses to neoadjuvant chemoimmunotherapy in ovarian carcinoma 3. In resectable non-small cell lung cancer, elevated post-treatment CD8B expression correlates with disease relapse following neoadjuvant chemoimmunotherapy 4. Additionally, CD8B shows signatures of positive selection in human populations, with evidence suggesting potential roles in human brain evolution 5. These findings establish CD8B as both a fundamental immune regulator and a valuable predictive marker for immunotherapy outcomes.