TY - JOUR
T1 - Harnessing the intestinal microbiome for optimal therapeutic immunomodulation
AU - Viaud, S.
AU - Daillère, R.
AU - Boneca, I. G.
AU - Lepage, P.
AU - Pittet, M. J.
AU - Ghiringhelli, F.
AU - Trinchieri, G.
AU - Goldszmid, R.
AU - Zitvoge, Laurence
PY - 2014/8/15
Y1 - 2014/8/15
N2 - Distinct cytotoxic agents currently used in the oncological armamentarium mediate their clinical benefit by influencing, directly or indirectly, the immune system in such a way that innate and adaptive immunity contributes to the tumoricidal activity. Now, we bring up evidence that both arms of anticancer immunity can be triggered through the intervention of the intestinal microbiota. Alkylating agents, such as cyclophosphamide, set up the stage for enhanced permeability of the small intestine, facilitating the translocation of selected arrays of Gram-positive bacteria against which the host mounts effector pTh17 cells and memory Th1 responses. In addition, gut commensals, through lipopolysaccharide and other bacterial components, switch the tumor microenvironment, in particular the redox equilibrium and the TNF production of intratumoral myeloid cells during therapies with platinum salts or intratumoral TLR9 agonists combined with systemic anti-IL10R Ab respectively. Consequently, antibiotics can compromise the efficacy of certain chemotherapeutic or immunomodulatory regimens.
AB - Distinct cytotoxic agents currently used in the oncological armamentarium mediate their clinical benefit by influencing, directly or indirectly, the immune system in such a way that innate and adaptive immunity contributes to the tumoricidal activity. Now, we bring up evidence that both arms of anticancer immunity can be triggered through the intervention of the intestinal microbiota. Alkylating agents, such as cyclophosphamide, set up the stage for enhanced permeability of the small intestine, facilitating the translocation of selected arrays of Gram-positive bacteria against which the host mounts effector pTh17 cells and memory Th1 responses. In addition, gut commensals, through lipopolysaccharide and other bacterial components, switch the tumor microenvironment, in particular the redox equilibrium and the TNF production of intratumoral myeloid cells during therapies with platinum salts or intratumoral TLR9 agonists combined with systemic anti-IL10R Ab respectively. Consequently, antibiotics can compromise the efficacy of certain chemotherapeutic or immunomodulatory regimens.
UR - http://www.scopus.com/inward/record.url?scp=84905970350&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-14-0987
DO - 10.1158/0008-5472.CAN-14-0987
M3 - Review article
C2 - 25074615
AN - SCOPUS:84905970350
SN - 0008-5472
VL - 74
SP - 4217
EP - 4221
JO - Cancer Research
JF - Cancer Research
IS - 16
ER -