Research has revealed a significant link between the microbiota and antitumor immunity, particularly in patients undergoing treatment for advanced cancers. This study focused on patients with advanced non-small cell lung cancer (NSCLC) and gastric cancer (GC) who received PD-1 blockade monotherapy using drugs such as nivolumab or pembrolizumab from March 2017 to September 2018. The findings suggest that the composition of gut microbiota may play a crucial role in modulating the immune response against tumors.
The research involved two distinct cohorts: a discovery cohort, which included 50 patients (15 with NSCLC and 35 with GC) who received PD-1 blockade monotherapy from March 2017 to December 2017, and a validation cohort with 21 patients (7 with NSCLC and 14 with GC) treated between January 2018 and September 2018. Additionally, patients with head and neck squamous cell carcinoma (HNSCC)—16 in total—who received similar treatments from June 2022 to October 2023 were included.
Researchers excluded patients who had undergone antibiotic treatments or microbiome interventions within the month preceding the start of therapy. This was to ensure that the microbiota’s influence on treatment response could be accurately assessed. Patients who exhibited a complete or partial response, or stable disease lasting more than six months, were classified as responders, while those who progressed on therapy were not.
To analyze the immune response, tumor-infiltrating lymphocytes (TILs) were isolated from tumor samples. These samples underwent a range of immunological analyses, including evaluations for PD-L1 expression, mismatch repair status, and the presence of Epstein-Barr virus. The study utilized advanced techniques such as flow cytometry and DNA sequencing to assess the implications of microbial diversity on immune responses.
According to the data, tumors that lacked specific mismatch repair markers were classified as deficient, which has implications for treatment outcomes. In the context of the microbiota, the research highlighted that specific bacterial compositions could potentially enhance the efficacy of PD-1 blockade therapies.
The methodology involved extensive sample collection and processing. Stool samples were collected shortly before treatment initiation, while fresh tumor samples were obtained via biopsy. Both types of samples were subjected to various analyses, including the sequencing of the 16S rRNA gene to assess bacterial diversity.
The study also focused on the potential of certain bacterial strains, such as YB328, in modulating the immune system. Researchers conducted in vitro and in vivo experiments using various mouse models to further elucidate the relationship between microbiota and immune responses. C57BL/6 and BALB/cJ mice were used for these experiments, which involved subcutaneous inoculations with cancer cells and subsequent treatments with PD-1 blockade antibodies.
Through multiple analyses, including RNA sequencing and quantitative PCR, the research sought to understand how specific bacterial strains could influence immune activation in cancer therapies. These findings not only shed light on the mechanisms of tumor immunity but also open new avenues for enhancing cancer treatment through microbiome modulation.
In conclusion, this research emphasizes the importance of microbiota in shaping antitumor immunity, particularly in patients undergoing PD-1 blockade therapy. The potential for integrating microbiome analysis into cancer treatment strategies could lead to more effective personalized therapies, ultimately improving patient outcomes in the battle against cancer.