5.4. Immune checkpoint blockade therapy

The problem of the therapeutic response variability was the starting point of recent researches which deal with the importance of microbiota in case of the patients treated with monoclonal antibodies involved in the immune checkpoint blockade.

Ipilimumab is an immunoglobulin G1 targeting the cytotoxic T-lymphocyte-associated protein 4 (CTLA4), which is a receptor protein involved in the immune checkpoint system and downregulation of the immune response.

The efficacy of the CTLA4 blockade was associated with T-lymphocyte responses induced by Bacteroides thetaiotaomicron and Bacteroides fragilis in both experimental models and human. No tumoral response was noticed after the treatment with ipilimumab in case of antibiotic treatment and germ-free mice. Exposure to B. fragilis, its polysaccharides, or its specific T cells reversed the response and favored the anticancer effect. The author of the study concluded that some Bacteroides spp. may play an important role and that the colitis may even antagonize the therapeutic efficacy [42].

Anti-PD-L1 is a monoclonal antibody successfully used for the treatment of several solid tumors, which target the protein programmed death-ligand 1 (PD-L1).

PD-L1 is a transmembrane protein, which acts as suppressor of the immune system and plays a role in escaping the cancer cells to immune system.

Sivan et al. demonstrated in their study that the commensal Bifidobacterium may have an unexpected role in enhancing antitumor immunity in vivo [43].

The authors used for research an experimental model of subcutaneous B16.SIY melanoma growth in genetically similar C57BL/6 mice. The animals were provided by two different animal facilities. After the anti-PD-L1 treatment, the results differ according to the animal provider. The Bifidobacterium spp. were identified by sequencing of the 16S ribosomal RNA and were correlated with the antitumor response therapy. The oral administration of bacteria improved tumor control to the same degree as anti-PD-L1, and the association of the microorganisms with this drug nearly abolished tumor outgrowth [22–43].
