Immuno-Oncology Technology

Source of T cells driving clinical response to ICB Whether the key mechanism underpinning ICB response is through driving novel T cells into tumours (termed ‘T-cell clonal replacement’) or reinvigoration of pre-existing TILs (termed ‘T-cell clonal revival’) is under debate ( Figure 3 ). 52 Pauken K.E. Lagattuta K.A. Lu B.Y. et al. TCR-sequencing in cancer and autoimmunity: barcodes and beyond.

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Highlights • CD47 is a “don’t eat me” signal overexpressed on cancer cells. • Blockade of the CD47–SIRPα signaling pathway leads to phagocytosis of tumor cells. • CD47–SIRPα blockade plus standard treatment shows promising clinical efficacy. • Clinically, CD47–SIRPα blockade plus standard treatment is well tolerated. • Clinical trials targeting CD47–SIRPα in hematologic and solid tumors are ongoing.

Highlights • CRISPR-Cas9 screens shed light on tumor-intrinsic mechanisms of immune sensitivity. • Different screen settings highlight tumor-intrinsic and environmental influences. • Effects of IFN-γ and antigen presentation pathways depend on environmental contexts. • Cellular context impacts how TNF and autophagy pathways affect immune sensitivity. • Potential therapeutic targets identified in the TNF, autophagy and IFN-γ pathways.