Four TME classes in NSCLC defined by immune composition in tumor nests and surrounding stroma. A, Tumor cores were classified into four TME classes, derived by clustering immune cell densities in the tumor nest and stroma. Only LUAD (n = 65 cores, 35 tumors) and LUSC (n = 48, 23 tumors) tumor cores are featured, and corresponding clinical annotations are displayed. Regional growth patterns are shown for LUAD: lepidic (low grade), acinar and papillary (mid-grade), solid and cribriform (high grade). B, TME classifications displayed separately for LUAD and LUSC. Numbers indicate the number of cores with a given TME class for each histology subtype. The barplot shows the total expressed neoantigen count for all predicted HLA alleles in the range 0–269 for LUAD and 23–160 for LUSC, colored by their clonal and subclonal status. Horizontal lines connect tumor cores from the same multiregion tumor (n = 33 tumors). The annotation bars display tumor genomic features and PD-L1 tumor cell (TC) staining (SP142 IHC) for the corresponding tumor cores. C, Composite images and cell type maps of representative examples for each TME class. Crop insets are 82 μm in diameter. D, A heat map of T values derived from an LMEM of the major cell type density across TME classes, adjusted for histology subtype as a fixed effect and patient as a random effect. Significant relationships are indicated with an asterisk for P ≤ 0.05. TIL, tumor-infiltrating lymphocyte; MΦ, macrophage; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; NSCLC, non–small cell lung cancer; TME, tumor microenvironment; TMB, tumor mutation burden; muts/Mb, mutations per megabase; panCK, pancytokeratin; LMEM, linear mixed effects model.
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Enfield et al. (2024) studied this question.
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