CD8B encodes the beta subunit of the CD8 coreceptor, which is essential for adaptive immunity and T cell development. In cytotoxic T lymphocytes, CD8B functions as a coreceptor that simultaneously engages the T cell receptor and MHC class I peptide complexes presented by antigen-presenting cells. This interaction recruits the Src kinase LCK to the TCR-CD3 complex, triggering intracellular signaling cascades that activate cytotoxic T cell responses, including lymphokine production and cell-mediated immunity. Palmitoylation of CD8B's cytoplasmic tail directs the CD8 heterodimer into plasma membrane lipid rafts, enriching signaling proteins at sites of T cell activation. CD8B also plays a critical role in thymic selection of CD8+ T cells during development 1. CD8B expression levels serve as a biomarker of tumor-infiltrating CD8 T cell abundance in cancer immunotherapy contexts. In patients with advanced solid tumors treated with anti-PD-1 or anti-PD-L1 monotherapy, a radiomic signature incorporating CD8B gene expression predicted response and improved overall survival 2. In resectable non-small cell lung cancer treated with neoadjuvant chemoimmunotherapy, higher post-treatment CD8B expression was associated with disease relapse, while baseline CD8B expression contributed to immune infiltration patterns predictive of complete pathological response 3. In high-grade ovarian carcinoma, the CD8B/FOXP3 expression ratio predicted response to neoadjuvant chemotherapy plus pembrolizumab with an area under the curve of 0.93 4. CD8B mutations and deficiencies are associated with immunodeficiency disorders, reflecting the gene's essential role in adaptive immune function.