Anti-PD-1 immunotherapy has a large impact on cancer treatment but the rate of positive treatment outcomes is 40-45% and depends on many factors. One of the factors affecting the outcome of immunotherapy is the gut microbiota composition. This effect has been demonstrated both in model objects and in clinical patients groups. However, in order to identify clear causal relationships between microbiota and anti-PD1 immunotherapy response, it is necessary to expand the number of patients and experimental samples. This work presents an analysis of metagenomic data obtained using whole-genome sequencing of stool samples from melanoma patients (n=45) with different responses to anti-PD1 therapy. The analysis of the differential representation of microbial species has shown a difference in the composition of the microbiota between the experimental groups. Results of this study indicate existence of a strong link between the composition of the gut microbiota and the outcome of anti-PD1 therapy. Expansion of similar research may help develop additional predictive tools for the outcome of anti-PD1 cancer immunotherapy, as well as increase its effectiveness.
Anti-PD1 immunoterapiia, napravlennaia na belok 1 programmiruemoĭ kletochnoĭ smerti (programmed cell death protein 1, PD1), okazala bol'shoe vliianie na lechenie raka, odnako protsent pozitivnykh iskhodov terapii sostavliaet 40-45% i zavisit ot mnozhestva faktorov. Odnim iz faktorov, vliiaiushchikh na iskhod immunoterapii, iavliaetsia sostav mikrobioty kishechnika. Dannyĭ éffekt byl prodemonstrirovan kak na model'nykh ob"ektakh, tak i na klinicheskikh gruppakh patsientov. Odnako dlia vyiavleniia chetkikh prichinno-sledstvennykh sviazeĭ mezhdu mikrobiotoĭ i otvetom na anti-PD1 immunoterapiiu neobkhodimo rasshiriat' kolichestvo vyborok i patsientov. V dannoĭ rabote predstavlen analiz metagenomnykh dannykh, poluchennykh v rezul'tate polnogenomnogo sekvenirovaniia obraztsov kala ot patsientov s melanomoĭ (n=45), kotorye davali razlichnyĭ otvet na anti-PD1 terapiiu. Analiz éksperimental'nykh dannykh prodemonstriroval razlichie v sostave mikrobioty mezhdu éksperimental'nymi gruppami. Poluchennye rezul'taty svidetel'stvuiut o nalichii sviazi mezhdu sostavom mikrobioty kishechnika i iskhodom anti-PD1 terapii. Rasshirenie issledovaniĭ v dannom napravlenii mozhet pomoch' razrabotat' dopolnitel'nye instrumenty predskazaniia iskhoda anti-PD1 immunoterapii raka, a takzhe povysit' ee éffektivnost'.
Keywords: gut microbiota; melanoma; microbial communities; whole genome metagenomic sequencing.