The HRS cell microenvironmental niche is enriched for CTLA-4–positive cells and CD86-positive TAMs. (A-C) Schematic showing generation of “HRS proximal” and distal regions in the representative case shown in Figure 4 (CHL12). (D) The HRS proximal region is enriched for T cells that are CTLA-4–positive (median percentage positive, 38%; range, 3%-84%) in each individual case, and across cases, relative to the distal region (median, 18%; range, 2%-53%; P = .0001). (E) The HRS proximal region is enriched for CD68-positive TAMs that are CD86-positive (median percentage positive, 38%; range, 22%-91%) in each individual case, and across cases, relative to the distal region (median percentage positive, 24%; range, 0%-69%; P = .0007). (F) The CD86-positive TAMs within 75 μm of HRS cells were predominantly PD-L1–positive (median percentage positive, 92%; range, 52%-99%) (PD-L1–positive vs PD-L1–negative, P = .002). EBV-positive cases are marked by asterisks.