NOD2 restrains probiotic-mediated TLR2-dependent antitumor immunity
The gut microbiota influences cancer immunotherapy, but how interactions among host microbial sensors determine the activity of individual bacteria remains unclear. Here, we show that NOD2 restrains TLR2-dependent antitumor immunity induced by Lactiplantibacillus plantarum. Oral administration of live or heat-killed L. plantarum enhanced immune checkpoint blockade efficacy in mouse tumor models.…
Recent research reveals that the gut microbiota plays a role in cancer immunotherapy, but the exact mechanisms by which host microbial sensors influence individual bacteria's activity are still unknown. In a study, researchers discovered that NOD2, a host microbial sensor, hinders TLR2-dependent antitumor immunity triggered by Lactiplantibacillus plantarum.
When L. plantarum was administered orally to mice with tumors, it enhanced the efficacy of immune checkpoint blockade therapy. This effect depended on the host's TLR2 signaling and was suppressed when bacterial lipoproteins were disrupted. Conversely, NOD2 deficiency boosted tumor control, interferon-associated pathways, and T cell activation.
Additionally, NOD2 deficiency amplified chemokine and interferon responses to L. plantarum and a TLR2 agonist called Pam3CSK4 in myeloid cells. By genetically eliminating or inhibiting NOD2, the researchers found that Pam3CSK4-mediated tumor control improved when used in combination with checkpoint blockade. These findings highlight NOD2 as a functional checkpoint in TLR2-driven antitumor immunity and demonstrate that interactions between host microbial-sensing pathways impact the therapeutic potential of commensal bacteria and innate immune agonists.
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