Local tumor microbial signatures and response to checkpoint blockade in non-small cell lung cancer
Maximilian Boesch1, Florent Baty1, Werner C Albrich2
1Lung Center, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
Abstract:
In cancer patients, the clinical response to checkpoint-based immunotherapy is associated with the composition and functional quality of the host microbiome. While the relevance of the gut microbiome for checkpoint immunotherapy outcome has been addressed intensively, data on the role of the local tumor microbiome are missing. Here, we set out to molecularly characterize the local non-small cell lung cancer microbiome using 16S rRNA gene amplicon sequencing of bronchoscopic tumor biopsies from patients treated with PD-1/PD-L1-targeted checkpoint inhibitors. Our analyses showed significant diversity of the tumor microbiome with high proportions of Firmicutes, Bacteroidetes and Proteobacteria. Correlations with clinical data revealed that high microbial diversity was associated with improved patient survival irrespective of radiology-based treatment response. Moreover, we found that the presence of Gammaproteobacteria correlated with low PD-L1 expression and poor response to checkpoint-based immunotherapy, translating into poor survival. Our study suggests novel microbiome-specific/derived biomarkers for checkpoint immunotherapy response prediction and prognosis in lung cancer. In a broader sense, our data draw attention to the local tumor microbial habitat as an important addition to the spatially separated microbiome of the gut compartment.
Insights
The tumor microbiome
Area of Science:
- Oncology
- Microbiome Research
- Immunotherapy
Background:
- Clinical response to immunotherapy in cancer patients is linked to the host microbiome.
- The gut microbiome's role in immunotherapy is well-studied, but the tumor microbiome's role remains unclear.
Purpose of the Study:
- To molecularly characterize the non-small cell lung cancer (NSCLC) tumor microbiome.
- To investigate the association between the tumor microbiome and response to PD-1/PD-L1 inhibitors.
Main Methods:
- 16S rRNA gene amplicon sequencing was performed on bronchoscopic tumor biopsies.
- Microbiome composition and diversity were analyzed.
- Correlations between microbial data and clinical outcomes were assessed.
Main Results:
- The NSCLC tumor microbiome exhibited significant diversity, with dominant phyla including Firmicutes, Bacteroidetes, and Proteobacteria.
- Higher microbial diversity in tumors correlated with improved patient survival, independent of radiological response.
- Presence of Gammaproteobacteria was associated with lower PD-L1 expression and poorer immunotherapy response and survival.
Conclusions:
- The tumor microbiome is a significant factor in NSCLC immunotherapy outcomes.
- Microbial diversity and specific taxa like Gammaproteobacteria may serve as biomarkers for predicting immunotherapy response and prognosis in lung cancer.
- The local tumor microbiome warrants consideration alongside the gut microbiome for understanding immunotherapy efficacy.
