In this first analysis, samples from 23 BC survivors (group 1) and 291 healthy female controls (group 2) were characterised through the V3 and V4 regions that encode the “16S rRNA” gene of each bacteria. The samples were sequenced by next-generation sequencing (NGS), and the taxonomy was identified by resorting to Kraken2 and improved with Bracken, using a curated database called ‘GutHealth_DB’. The α and β-diversity analyses were used to determine the richness and evenness of the gut microbiota. A non-parametric Mann-Whitney U test was applied to assess differential abundance between both groups. The Firmicutes/Bacteroidetes (F/B) ratio was calculated using a Kruskal-Wallis chi-squared test. The α-diversity was significantly higher in group 1 (p = 0.28 × 10−12 for the Chao index and p = 1.64 × 10−12 for the ACE index). The Shannon index, a marker of richness and evenness, was not statistically different between the two groups (p = 0.72). The microbiota composition was different between the two groups: a null hypothesis was rejected for PERMANOVA (p = 9.99 × 10−5) and Anosim (p = 0.04) and was not rejected for β-dispersion (p = 0.158), using Unifrac weighted distance. The relative abundance of 14 phyla, 29 classes, 25 orders, 64 families, 116 genera, and 74 species differed significantly between both groups. The F/B ratio was significantly lower in group 1 than in group 2, p < 0.001. Our study allowed us to observe significant taxonomic disparities in the two groups by testing the differences between BC survivors and healthy controls. Additional studies are needed to clarify the involved mechanisms and explore the relationship between microbiota and BC survivorship.

The treatment paradigm of neoplastic diseases has dramatically shifted with the introduction of immune checkpoint inhibitors (ICI). They induce a durable response in a wide variety of solid tumors, but this response depends on the infiltration of lymphocytes capable of recognizing and killing tumor cells. The primary predictor of intrinsic immune resistance to ICIs is the absence of lymphocytes in the tumor, the so-called “cold tumors”. Colorectal cancer (CRC) remains one of the most common and challenging cancer, but it is not traditionally considered a highly immunogenic tumor. In fact, immunotherapy showed a remarkable antitumoral activity only on a small subset of CRC patients – the ones with microsatellite instability-high/deficient DNA mismatch repair (MSI-H/dMMR). Most CRCs display a molecular microsatellite stability/proficient DNA mismatch repair (MSS/pMMR) profile, so strategies to improve tumor immunogenicity are crucial. Therefore, ongoing studies investigate new approaches to convert “cold” to “hot” tumors in MSS/pMMR CRCs. In addition, it has been described that gut microbiota influences tumor development and the host immune response. Hence, the microbiota may modulate the immune response, becoming a promising biomarker to identify patients who will benefit from ICIs. Future data will help to better understand microbiota mechanisms and their role in ICI efficacy. Precision medicine in cancer treatment could involve modulation of the microbiota through different strategies to improve tumor immunogenicity. In this review, we aim to present the potential relationship between gut microbiota and the modulation of the immune system and the hypothetical implications in CRC treatment, namely ICIs.

No abstract

No abstract

No abstract