Extended Data Fig. 9: Schematic model of P. anaerobius-driven anti-PD1 resistance in CRC and potential therapeutic approaches. | Nature Microbiology

Extended Data Fig. 9: Schematic model of P. anaerobius-driven anti-PD1 resistance in CRC and potential therapeutic approaches.

From: Peptostreptococcus anaerobius mediates anti-PD1 therapy resistance and exacerbates colorectal cancer via myeloid-derived suppressor cells in mice

Extended Data Fig. 9

P. anaerobius engaged with CRC cells via integrin α2/β1 receptor to promote nuclear translocation of NF-κB p65, which in turn stimulates release of CXCL1 to recruit CXCR2+ MDSCs to tumours. In addition, lytC_22 protein secreted from P. anaerobius directly activates Slamf4 receptor on MDSCs, leading to elevated arginase 1 (Arg1) and iNOS expression. P. anaerobius infection thus increased MDSCs accumulation and activation, leading to suppression of CD8+ T cells and non-response to anti-PD1 therapy. Blockade of integrin α2/β1 or Slamf4 could interrupt this process to impair MDSCs in tumour microenvironment and reactivate IFNγ expressing CD8+ T cells to overcome P. anaerobius-driven anti-PD1 resistance.

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