Nat Med: Intestinal microbiome characteristics are related to the toxicity of CTLA-4 and PD-1 combined blocking therapy

Previous studies have shown that immune checkpoint blocking combination therapy (CICB) for CTLA-4 and PD-1 is associated with a high objective response rate in patients, but a large proportion of patients experience immune-related adverse events (irAE) .

Interestingly, the patient's clinical response rate and irAE seem to be related, and the relevant molecular mechanism of treatment toxicity is currently unclear
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Combination therapy for CTLA-4 and PD-1 immune checkpoint blockade (CICB) is associated with a high objective response rate in patients, but a large proportion of patients experience immune-related adverse events (irAE)
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Combination therapy for CTLA-4 and PD-1 immune checkpoint blockade (CICB) is associated with a high objective response rate in patients, but a large proportion of patients experience immune-related adverse events (irAE)

Therefore, it is necessary to deeply understand the relevant biomarkers of CICB treatment, the patient's response to CICB and the related mechanisms of drug toxicity
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It is necessary to deeply understand the relevant biomarkers of CICB treatment, the patient's response to CICB and the related mechanisms of drug toxicity
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It is necessary to deeply understand the relevant biomarkers of CICB treatment, the patient's response to CICB and the related mechanisms of drug toxicity

In order to solve the above problems, the researchers analyzed the blood, tumor tissue and gut microbiome of 77 patients with advanced melanoma treated with CICB, and conducted parallel studies in a preclinical model
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Analysis of molecular and immune predictors of patient response to treatment

Analysis of molecular and immune predictors of patient response to treatment

The results showed that the incidence of any immune-related adverse events ≥ grade 3 was high (49%)
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Tumor-related immune and genomic biomarkers in response to CICB treatment are similar to those identified in ICB monotherapy, and the researchers found that the toxicity of CICB is related to a more diverse peripheral T cell pool

The incidence of any immune-related adverse events ≥ grade 3 is high (49%)

Correlation between gut microbes and CICB response

Correlation between gut microbes and CICB response

All in all, the results of this study provide a potential new therapeutic strategy for targeting CICB toxicity
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The results of this study provide a potential new therapeutic strategy for targeting CICB toxicity
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The results of this study provide a potential new therapeutic strategy for targeting CICB toxicity

Gut microbiota signatures are associated with toxicity to combined CTLA-4 and PD-1 blockade.

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