The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy.
Havel JJ, Chowell D, Chan TA
Nat Rev Cancer. Mar 2019. doi: 10.1038/s41568-019-0116-x
Anticancer immunotherapy treatments based on checkpoint inhibitors (ICI) are getting more and more important. For example, antibodies targeting the proteins PD1-PDL1 have been aproved by the FDA as first or second-line treatments for several kinds of cancers.
However, even though these kind of treatments drastically improve the life expentancy of the patients that benefit from them most of the patients receiving ICI do not show any benefit at all. It is thus of great importance having predictive biomarkers of ICI efficacy.
This review summarizes the current knowledge of several factors that might play a role in the ICI efficacy like the tumor mutation burden, self-antigen expression, patient tumor and germline genetics, somatic copy number variations. Of particular interest, It highlights the importance of the commensal microbiota as a predictive biomarker. The authors review four independent studies that find relation between gut microbiota and ICI response in melanoma, NSCLC (non-small-cell lung cancer), RCC (renal cell cancer) and urothelial cancer.
Studies show that certain organisms might contribute to ICI response even though there are differences in the detected organisms in the four studies
Although there is some overlap between the four reports, each study identified different strains of bacteria that associate with response or resistance. The reasons for these variable results are not immediately apparent but may include differences in microbial sequencing and analysis techniques as well as geographic variations in the distribution of gut flora. Nonetheless, in each case, adoptive transfer of response-associated bacteria to germ-free or antibiotic-treated mice was able to confer ICI sensitivity, suggesting that the identified bacteria were sufficient to promote ICI response.
And that, in general, higher gut microbiome diversity positively correlates with ICI response
Furthermore, increased microbiota diversity, irrespective of species identity, was associated with improved ICI response in humans. Notably, one study found that the ratio of response-associated (‘good’) to resistance-associated (‘bad’) bacteria was able to clearly stratify responders from non-responders