The Immune Landscape of Cancer

Abstract

We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes-wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-β dominant-characterized by differences in macrophage or lymphocyte signatures, Th1:Th2 cell ratio, extent of intratumoral heterogeneity, aneuploidy, extent of neoantigen load, overall cell proliferation, expression of immunomodulatory genes, and prognosis. Specific driver mutations correlated with lower (CTNNB1, NRAS, or IDH1) or higher (BRAF, TP53, or CASP8) leukocyte levels across all cancers. Multiple control modalities of the intracellular and extracellular networks (transcription, microRNAs, copy number, and epigenetic processes) were involved in tumor-immune cell interactions, both across and within immune subtypes. Our immunogenomics pipeline to characterize these heterogeneous tumors and the resulting data are intended to serve as a resource for future targeted studies to further advance the field.

AVNP2 protects against cognitive impairments induced by C6 glioma by suppressing tumour associated inflammation in rats

“…It is universally accepted that glioma-secreted soluble factors and TME-secreted soluble factors all take part in the formation of the TME, and promote the proliferation of tumour cells (Barkal et al, 2019). What has been mentioned is that much research has focused on the micro-environment inside the glioma itself (Thorsson et al, 2018;Platten et al, 2018). However, peri-tumour inflammation is worth observing too, which happens in the normal brain region and directly influences normal brain function.…”

Treatment-naïve HPV+ head and neck cancers display a T-cell-inflamed phenotype distinct from their HPV- counterparts that has implications for immunotherapy

“…48 Only those HNSCC samples with a CIBERSORT p < 0.01 were included in our analysis, which resulted in 28 HPV+, 209 HPV-, and 17 normal control samples used in this analysis. The total leukocyte fraction was also previously reported for all TCGA samples as part of the Pan-Cancer Atlas.…”

Immunological and classical subtypes of oral premalignant lesions

“…37 Finally, a recent pancancer study from TCGA has reported 6 immune subtypes that encompass multiple cancer types. 38 The vast majority of HNSCC fits into the wound healing (more frequent in the classical subtype) or the IFN-gamma dominant subtypes that do not completely overlap with previously described subtypes. Whether the immunological subtype of OPL precedes transformation to the IFN-gamma subtype and the classical subtype of OPL precedes transformation to the wound healing and classical subtypes is a plausible hypothesis that remains to be demonstrated through the analysis of OPL and subsequent paired oral squamous cell carcinoma.…”