Immune spatial balance in LUSC. Spatial positioning of immune rich areas can reflect an immunosuppressive or an immunostimulant microenvironment. Increased intratumoral IH compared with peritumoral IH may reflect an immunosuppressive TME, characterized by decreased TLS abundance, lower densities of CD20+CXCR5+, and CD79b+ B-cell densities, decreased interactions between CD20+CXCR5+ B cells and CD4+ T cells, and the presence of a negative correlation between CD8+ T-cell and Treg cell abundance. Also, high ratio of intratumoral IH is coupled with increased B-cell and Treg infiltration in the whole tumor. Cancer hotspots, peritumoral IHs, and intratumoral IHs are denoted by red, blue, and green colors, respectively. An IH can consist of peritumoral and intratumoral compartments, denoted as circles with a combination of green and blue.