TY - JOUR
T1 - Concepts Collide
T2 - Genomic, immune, and microbial influences on the tumor microenvironment and response to cancer therapy
AU - Andrews, Miles C.
AU - Reuben, Alexandre
AU - Gopalakrishnan, Vancheswaran
AU - Wargo, Jennifer A.
N1 - Publisher Copyright:
© 2018 Andrews, Reuben, Gopalakrishnan and Wargo.
PY - 2018/5/4
Y1 - 2018/5/4
N2 - Cancer research has seen unprecedented advances over the past several years, with tremendous insights gained into mechanisms of response and resistance to cancer therapy. Central to this has been our understanding of crosstalk between the tumor and the microenvironment, with the recognition that complex interactions exist between tumor cells, stromal cells, overall host immunity, and the environment surrounding the host. This is perhaps best exemplified in cancer immunotherapy, where numerous studies across cancer types have illuminated our understanding of the genomic and immune factors that shape responses to therapy. In addition to their individual contributions, it is now clear that there is a complex interplay between genomic/epigenomic alterations and tumor immune responses that impact cellular plasticity and therapeutic responses. In addition to this, it is also now apparent that significant heterogeneity exists within tumors-both at the level of genomic mutations as well as tumor immune responses-thus contributing to heterogeneous clinical responses. Beyond the tumor microenvironment, overall host immunity plays a major role in mediating clinical responses. The gut microbiome plays a central role, with recent evidence revealing that the gut microbiome influences the overall immune set-point, through diverse effects on local and systemic inflammatory processes. Indeed, quantifiable differences in the gut microbiome have been associated with disease and treatment outcomes in patients and pre-clinical models, though precise mechanisms of microbiome-immune interactions are yet to be elucidated. Complexities are discussed herein, with a discussion of each of these variables as they relate to treatment response.
AB - Cancer research has seen unprecedented advances over the past several years, with tremendous insights gained into mechanisms of response and resistance to cancer therapy. Central to this has been our understanding of crosstalk between the tumor and the microenvironment, with the recognition that complex interactions exist between tumor cells, stromal cells, overall host immunity, and the environment surrounding the host. This is perhaps best exemplified in cancer immunotherapy, where numerous studies across cancer types have illuminated our understanding of the genomic and immune factors that shape responses to therapy. In addition to their individual contributions, it is now clear that there is a complex interplay between genomic/epigenomic alterations and tumor immune responses that impact cellular plasticity and therapeutic responses. In addition to this, it is also now apparent that significant heterogeneity exists within tumors-both at the level of genomic mutations as well as tumor immune responses-thus contributing to heterogeneous clinical responses. Beyond the tumor microenvironment, overall host immunity plays a major role in mediating clinical responses. The gut microbiome plays a central role, with recent evidence revealing that the gut microbiome influences the overall immune set-point, through diverse effects on local and systemic inflammatory processes. Indeed, quantifiable differences in the gut microbiome have been associated with disease and treatment outcomes in patients and pre-clinical models, though precise mechanisms of microbiome-immune interactions are yet to be elucidated. Complexities are discussed herein, with a discussion of each of these variables as they relate to treatment response.
KW - Biomarkers
KW - Cancer genomics
KW - Cancer immunotherapy
KW - Heterogeneity
KW - Microbiome
KW - Systemic immunity
KW - Tumor microenvironment
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U2 - 10.3389/fimmu.2018.00946
DO - 10.3389/fimmu.2018.00946
M3 - Review article
C2 - 29780391
AN - SCOPUS:85046621687
SN - 1664-3224
VL - 9
JO - Frontiers in immunology
JF - Frontiers in immunology
IS - MAY
M1 - 946
ER -