Recently, the relationship between cancer, microbiota, and oncologic treatments, especially immunotherapy, has raised the interest of the scientific community.

Several data suggest that cancer development is closely related to the disruption of the biological balance between the immune system and the gut flora community. Gut microbiota regulates epithelial mucosa homeostasis, host immunity and physiological metabolism, and dysbiosis is involved in the development of many diseases, including neoplasms (Roy and Trinchieri, 2017). Microorganisms in the local tumor environment can contribute to the onset of cancer, challenging the traditional belief that some organs are sterile.

Microbiota also play an active role in cancer cell proliferation and epithelial-mesenchymal transition (EMT), mediating the processes of carcinogenesis and recurrence. Cancer cells could acquire the ability of immunoediting, which leads to bypass the immunosurveillance and escape the physiological immune mechanism of preventing uncontrolled proliferation and metastasis (Quail and Joyce, 2013). The intestinal microbes could also influence the outcome of cancer treatments, either by modifying the clinical efficacy of treatments or by favoring the development of adverse events (AEs), due to their interaction with the host's immune system, modulation of host inflammation and immune microenvironment and alteration of drug metabolism (Roy and Trinchieri, 2017, Panebianco et al., 2018).

Several factors can alter microbiota, modulate the tumor microenvironment, and influence the effectiveness of therapies. Cancer therapies may modulate microbiota, either by inducing dysbiosis or by affecting inflammation, local and systemic immune response. Immune checkpoints inhibitors (ICIs) target crucial pathways that regulate the immune response, preventing the autoimmunity. However, ICIs clinical effectiveness is highly variable across different cancer types and even across different patients within the same setting (Bagchi et al., 2021).

Several biomarkers have been investigated to predict response to ICIs: high tumor mutational burden (TMB), microsatellite instability (MSI), high expression of PD-L1, and high tumor inflammatory state. Novel studies could determine which microbial species and critical concentrations may improve the outcome of cancer therapy to help clinicians promoting an increasingly personalized approach to therapy (Wang et al., 2020). Recent studies investigated the role of fecal microbiome transplant (FMT), with the aim of modulating the composition and diversity of gut microbiome in patients with refractory cancers, to improve ICIs efficacy (Oh et al., 2021).

There are some external factors that can differently modulate the microbiota, such as use of antibiotics, proton pump inhibitors treatment (PPI), lifestyle, or the use of prebiotics/probiotics (Fig. 1). The administration of antibiotics within the two-three months before or after the initiation of immunotherapy is associated with decreased survival rates and shortened progression-free survival (PFS), due to loss of microbiota homeostasis, effects on host tissues, and enhanced activity of resistant microorganisms (Tsikala-Vafea et al., 2021). PPI treatment leads to significantly worse outcomes in patients with advanced cancer, treated by ICIs, due to the interference with microbiota’s diversity (Lopes et al., 2023). Patients’ lifestyle may have an important impact on gut microbiota, by modulating the levels of metabolic and inflammatory biomarkers, the expression of PD-L1, and the types of commensal microorganisms. The use of prebiotics/probiotics, could be able to mediate the immune response by regulating the expression of cytokines and interleukins, affecting both clinical outcome and AEs (Garczyk et al., 2022).

In synthesis, the characterization of gut and local microbiota may lead to identify a new predictive biomarker for oncologic treatments, especially for immunotherapy, and a new target for treatment optimization.

The aims of this review are to provide a current snapshot of the state of art regarding gut and local microbiota in oncology and the most relevant studies, concluded and ongoing (Table 1. - updated to March 2023), investigating its potential clinical value in the principal tumor types.