Immunospatial tumor microenvironment analysis identifies B cell aggregates associated with recurrence-free survival in primary melanoma

Abstract The complex spatial cellular interactions of immune cell populations within melanoma can provide insight into immune functions occurring within tumors. Tertiary lymphoid structures (TLSs) and B cell aggregates (BssCAs) are key features in the immunospatial tumor microenvironment (isTIME), yet are difficult to accurately detect and are poorly understood in primary melanoma. This study utilized mIHC and novel spatial analysis methods to characterize the isTIME of primary melanomas to identify associations between T cells, B cells, NK cells, Langerhans cells and patient outcome. Spatial profiling of 55 primary melanomas identified that immune neighborhood metaclusters (NMCs) enriched for either B cells, CD39+CD103+ CD8+ T cells or Langerhans cells were associated with improved rates of 5-year recurrence-free survival (RFS), while a BCA subtype harboring CD103-PD-1+ CD8+ T cells was associated with melanoma recurrence. Further analysis revealed that BCAs with higher proportions of CXCL13+ B cells were linked with reduced Breslow thickness and absence of ulceration in the primary tumor. Furthermore, the polarization of the isTIME toward B cell rather than CD38+ cell-dominant BCAs was associated with reduced ulceration and a smaller Breslow thickness. This study highlights the significance of immune neighborhoods containing CD39+CD103+ CD8+ T cells, CXCL13 expression in BCAs and their polarization as prognostic indicators in primary melanoma.