Tregs and resting CD4+ memory T cells were more infiltrated in subtype A, whereas CD8+ T cells, gamma delta T cells, and CD4+ memory-activated T cells were more infiltrated in subtype B. Similarly, the immune infiltration ssGSEA scores in TCGA-DLBCL and the pathological slide data showed a higher immune infiltration in cluster B. In the subsequent drug sensitivity prediction analysis, subgroup A exhibited resistance to doxorubicin, bleomycin, etoposide, elesclomol, and cisplatin. Here, CD8A is linked to diffuse large B-cell lymphoma.