Compared to non-HIV cHL, the TME in HIV-associated cHL is enriched with CD68+ and CD163+ spindle-shaped M2 macrophages, PD-L1-expressing cells, and Galectin-1 and significantly lower levels of CD4+ T-cells, CD56+ NK cells, CD57+ cells, CD123+ dendritic cells, and B cells in the TME of HIV-positive cHL cases compared to HIV-negative ones, fostering a highly immunosuppressive environment that shields HRS cells from immune attack [101,108,109,110,111]. This evidence concerns the gene NCAM1 and classic Hodgkin lymphoma.