Cancer. NW is a recipient of a Post-doctoral fellowship from the Agence Nationale de la Recherche. AS was supported by BMSI YIG 2014. FG is supported by SIgN core funding. LZ, IC, IGB are all sponsored by Association pour la Recherche contre le Cancer (PGA120140200851). FC was supported by INCA-DGOS (GOLD H78008.Nc was supported by INCA-DGOS (GOLD study; 2012-1-RT-14-IGR-01) LOreal awarded a prize to MV. We are grateful to the staff of the animal facility of Gustave Roussy and Institut Pasteur. We thank P. Gonin, B. Ryffel, T. Angelique, N. Chanthapathet, H. Li and S. Zuberogoitia for technical help LZ, MV and PL have filed patent applications n EP 14190167 that relates to specific topic: Methods and products for modulating microbiota composition for improving the efficacy of a cancer treatment with an immune checkpoint blocker Authors'contribution: MV performed experiments and analyzed results represented in Fig 2C-D, 3A left panel, 4A-B and Supplemental Fig 1B, 5CDE, 7, 8A,9, 10, 12, 13C-E-F-G, 14B 15, 16C, 17C, 21A-B, 22 and Supplemental Table 2(alone or helped by R+ TY+ NJ+ SB+ MPR+ BR), JMP(helped by PO and VPC) assessed gut pathology and generated Fig 3A middle and right panels as well as Supplemental Fig. 2, 5A-B, 13D, 17, 18, 19 and 21C, CF+ SR+ Mv did the experiments for Fig. 3D-E and Supplemental Fig. 11, SF(and eg) provided the patients specimen for the analyses of Fig. 3D-E and Supplemental Fig. 11, MC and Nw performed the FISH analyses, Ki67, cCasp3 and MUC2 staining and qPCR experiments represented in Fig 2A and Supplemental Fig. 4, 6, 8B-C. PL analyzed the 16s rrNa gene sequencing of mouse and human stools and described the PCA(Fig. 2C, Supplemental Fig 21A and Supplemental Table 1). SC and ge provided the tools and mice to analyze CtlA4 expression on gut T cells and ILCS represented in Supplemental Fig. 16A-B. AS and FG performed the flow cytometry analyses on LP DC subsets in Supplemental Fig. 13A-B. SM performed FITC dextran experiments depicted in Supplemental Fig 3. CD, VPC and AR cultured the enteroids and studied the IEC-IEL cross talk represented in Fig. 2B. MPR and Br(helped by SB) performed experiments depicted in Fig. 4C and Supplemental Fig IA. MPR and SB executed and analyzed results of QPCR from FMT experiments represented in Fig. 4D-E and Supplemental Fig 20 B- C. BR generated Supplemental Table 3 and 4 of patient characteristics. DR, MC, MB and IGB provided il-10, nod2, il-10/nod2, tlr2 deficient mice as well as germ-free mice and bacterial species of interest(B, BL, E. coli, E. faecalis L. plantarum for IGB and Bc for DR). PLW and EC characterized cultivable bacteria and performed mass spectrometry on bacterial species or isolates JN purified PS and bacterial capsule materials. LZ, MV and JMP wrote the manuscript CR, NC, CM and FC provided melanoma patients feces for FMT. GK and AE edited and critically reviewed the manuscript. LZ conceived the project and the experimental settings Materials Methods Patient and cohort characteristics. All clinical studies were conducted after informed consent of the patients, following the guidelines of the Declaration of Helsinki. Patient characteristics are detailed in Supplemental tables 3 and 4. Peripheral blood mononuclear cells(PBMC)were provided by Gustave Roussy Cancer Campus(Villejuif, France) and by the Department of Radiation Oncology(New York University [NYU], New York, NY, USA). Patients were2 ƒ…‡Ǥ  ‹• ƒ ‡…‹’‹‡ ‘ˆ ƒ ‘•Ǧ†‘…‘ƒŽ ˆ‡ŽŽ‘™•Š‹’ ˆ‘ Š‡ ‰‡…‡ ƒ‹‘ƒŽ‡ †‡ Žƒ ‡…Š‡…Š‡Ǥ™ƒ••’’‘‡†„› ʹͲͳͶǤ ‹••’’‘‡†„›‰…‘‡ˆ†‹‰Ǥǡ ǡ   ƒ‡ ƒŽŽ •’‘•‘‡† „› ••‘…‹ƒ‹‘ ’‘ Žƒ ‡…Š‡…Š‡ …‘‡ Ž‡ ƒ…‡ ȋ ͳʹͲͳͶͲʹͲͲͺͷͳȌǤ  ™ƒ• •’’‘‡† „› Ǧ  ȋ  ͹ͺͲͲͺȌǤ ™ƒ• •’’‘‡†„›Ǧ ȋ •†›ǢʹͲͳʹǦͳǦǦͳͶǦ ǦͲͳȌǤǯ‡ƒŽƒ™ƒ†‡†ƒ’‹œ‡‘ Ǥ‡ƒ‡‰ƒ‡ˆŽ‘Š‡•ƒˆˆ‘ˆŠ‡ƒ‹ƒŽˆƒ…‹Ž‹›‘ˆ •ƒ‡‘••›ƒ†•‹ƒ•‡Ǥ ‡ ŠƒǤ ‘‹ǡǤ›ˆˆ‡ŽǡǤ‰‡Ž‹‡ǡǤŠƒŠƒ’ƒŠ‡ǡǤ‹ƒ†Ǥ„‡‘‰‘‹‹ƒ ˆ‘ ‡…Š‹…ƒŽŠ‡Ž’Ǥǡƒ†Šƒ‡ˆ‹Ž‡†’ƒ‡ƒ’’Ž‹…ƒ‹‘•ιͳͶͳͻͲͳ͸͹Šƒ‡Žƒ‡•‘ •’‡…‹ˆ‹…‘’‹…ǣ‡Š‘†•ƒ†’‘†…•ˆ‘‘†Žƒ‹‰‹…‘„‹‘ƒ…‘’‘•‹‹‘ˆ‘‹’‘‹‰ Š‡‡ˆˆ‹…ƒ…›‘ˆƒ…ƒ…‡‡ƒ‡™‹Šƒ‹‡…Š‡…’‘‹„Ž‘…‡Ǥ Authors’ contribution: MV performed experiments and analyzed results represented in Fig. 1, 2C-D, 3A left panel, 4A-B and Supplemental Fig. 1B, 5CDE, 7, 8A, 9, 10, 12, 13C-E-F-G, 14B, 15, 16C, 17C, 21A-B, 22 and Supplemental Table 2 (alone or helped by RD + TY + NJ + SB + MPR + BR), JMP (helped by PO and VPC) assessed gut pathology and generated Fig 3A middle and right panels as well as Supplemental Fig. 2, 5A-B, 13D, 17, 18, 19 and 21C, CF + SR + MV did the experiments for Fig. 3D-E and Supplemental Fig. 11, SF (and EG) provided the patients specimen for the analyses of Fig. 3D-E and Supplemental Fig. 11, MC and NW performed the FISH analyses, Ki67, cCasp3 and MUC2 staining and qPCR experiments represented in Fig. 2A and Supplemental Fig. 4, 6, 8B-C. PL analyzed the 16S rRNA gene sequencing of mouse and human stools and described the PCA (Fig. 2C, Supplemental Fig.21A and Supplemental Table 1). SC and GE provided the tools and mice to analyze CTLA4 expression on gut T cells and ILCs represented in Supplemental Fig. 16A-B. AS and FG performed the flow cytometry analyses on LP DC subsets in Supplemental Fig. 13A-B. SM performed FITC dextran experiments depicted in Supplemental Fig. 3. CD, VPC and AR cultured the enteroids and studied the IEC-IEL cross talk represented in Fig. 2B. MPR and BR (helped by SB) performed experiments depicted in Fig. 4C and Supplemental Fig. 1A. MPR and SB executed and analyzed results of QPCR from FMT experiments represented in Fig. 4D-E and Supplemental Fig. 20 B￾C. BR generated Supplemental Table 3 and 4 of patient characteristics. DR, MC, MB and IGB provided il-10, nod2, il-10/nod2, tlr2 deficient mice as well as germ-free mice and bacterial species of interest (Bf, Bt, E. coli, E. faecalis L. plantarum for IGB and Bc for DR). PLW and EC characterized cultivable bacteria and performed mass spectrometry on bacterial species or isolates. JN purified PS and bacterial capsule materials. LZ, MV and JMP wrote the manuscript. CR, NC, CM and FC provided melanoma patients feces for FMT. GK and AE edited and critically reviewed the manuscript. LZ conceived the project and the experimental settings. Materials & Methods Patient and cohort characteristics. All clinical studies were conducted after informed consent of the patients, following the guidelines of the Declaration of Helsinki. Patient characteristics are detailed in Supplemental tables 3 and 4. Peripheral blood mononuclear cells (PBMC) were provided by Gustave Roussy Cancer Campus (Villejuif, France) and by the Department of Radiation Oncology (New York University [NYU], New York, NY, USA). Patients were