Paper - Review

DOI: 10.1038/s41467-018-05570-1

Abstract

The nature & extent of (immune cell infiltration)
← into solid tumors
→ are key determinants ←of therapeutic response

❗: report → integrated analysis of (1⃣ tumor composition 2⃣ genomics)
← across a wide spectrum of solid cancers
→ using a DNA methylation-based approach
→ to tumor cell fraction deconvolution

❗: identify two distinct tumor subgroups
→ 1⃣ immune hot 2⃣ immune cold
← display differing 1⃣ prognosis 2⃣ mutation burden 3⃣ cytokine signaling 4⃣ cytolytic activity 5⃣ oncogenic driver events

❗: demonstrate → the existence of such tumor subgroups pan-cancer
❗: link clonal-neoantigen burden → to cytotoxic T-lymphocyte infiltration
∴ Transcriptional signatures ← of hot tumors
→ are selectively engaged ← in immunotherapy responders

❗: treatment-naïve hot tumors are markedly enriched ↑
→ for known immune-resistance genomic alterations
∴ the heterogeneity of 1⃣ immunotherapy response 2⃣ prognosis → seen within this group

❗: define → a catalogue of (mediators of active anti-tumor immunity)
→ deriving 1⃣ candidate biomarkers 2⃣ potential targets → for precision immunotherapy

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