TY - JOUR
T1 - Comprehensive analyses of tumor immunity
T2 - Implications for cancer immunotherapy
AU - Li, Bo
AU - Severson, Eric
AU - Pignon, Jean Christophe
AU - Zhao, Haoquan
AU - Li, Taiwen
AU - Novak, Jesse
AU - Jiang, Peng
AU - Shen, Hui
AU - Aster, Jon C.
AU - Rodig, Scott
AU - Signoretti, Sabina
AU - Liu, Jun S.
AU - Liu, X. Shirley
N1 - Funding Information:
This work was supported by NCI 1U01 CA180980 (to X.S.L.), National Natural Science Foundation of China 31329003 (to X.S.L.), and Chinese Scholarship council fellowship (to T.L.).
Publisher Copyright:
© 2016 The Author(s).
PY - 2016/8/22
Y1 - 2016/8/22
N2 - Background: Understanding the interactions between tumor and the host immune system is critical to finding prognostic biomarkers, reducing drug resistance, and developing new therapies. Novel computational methods are needed to estimate tumor-infiltrating immune cells and understand tumor-immune interactions in cancers. Results: We analyze tumor-infiltrating immune cells in over 10,000 RNA-seq samples across 23 cancer types from The Cancer Genome Atlas (TCGA). Our computationally inferred immune infiltrates associate much more strongly with patient clinical features, viral infection status, and cancer genetic alterations than other computational approaches. Analysis of cancer/testis antigen expression and CD8 T-cell abundance suggests that MAGEA3 is a potential immune target in melanoma, but not in non-small cell lung cancer, and implicates SPAG5 as an alternative cancer vaccine target in multiple cancers. We find that melanomas expressing high levels of CTLA4 separate into two distinct groups with respect to CD8 T-cell infiltration, which might influence clinical responses to anti-CTLA4 agents. We observe similar dichotomy of TIM3 expression with respect to CD8 T cells in kidney cancer and validate it experimentally. The abundance of immune infiltration, together with our downstream analyses and findings, are accessible through TIMER, a public resource at http://cistrome.org/TIMER. Conclusions: We develop a computational approach to study tumor-infiltrating immune cells and their interactions with cancer cells. Our resource of immune-infiltrate levels, clinical associations, as well as predicted therapeutic markers may inform effective cancer vaccine and checkpoint blockade therapies.
AB - Background: Understanding the interactions between tumor and the host immune system is critical to finding prognostic biomarkers, reducing drug resistance, and developing new therapies. Novel computational methods are needed to estimate tumor-infiltrating immune cells and understand tumor-immune interactions in cancers. Results: We analyze tumor-infiltrating immune cells in over 10,000 RNA-seq samples across 23 cancer types from The Cancer Genome Atlas (TCGA). Our computationally inferred immune infiltrates associate much more strongly with patient clinical features, viral infection status, and cancer genetic alterations than other computational approaches. Analysis of cancer/testis antigen expression and CD8 T-cell abundance suggests that MAGEA3 is a potential immune target in melanoma, but not in non-small cell lung cancer, and implicates SPAG5 as an alternative cancer vaccine target in multiple cancers. We find that melanomas expressing high levels of CTLA4 separate into two distinct groups with respect to CD8 T-cell infiltration, which might influence clinical responses to anti-CTLA4 agents. We observe similar dichotomy of TIM3 expression with respect to CD8 T cells in kidney cancer and validate it experimentally. The abundance of immune infiltration, together with our downstream analyses and findings, are accessible through TIMER, a public resource at http://cistrome.org/TIMER. Conclusions: We develop a computational approach to study tumor-infiltrating immune cells and their interactions with cancer cells. Our resource of immune-infiltrate levels, clinical associations, as well as predicted therapeutic markers may inform effective cancer vaccine and checkpoint blockade therapies.
KW - Cancer immunity
KW - Cancer immunotherapies
KW - Cancer vaccine
KW - Checkpoint blockade
KW - Tumor immune infiltration
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U2 - 10.1186/s13059-016-1028-7
DO - 10.1186/s13059-016-1028-7
M3 - Article
C2 - 27549193
AN - SCOPUS:84983347823
SN - 1474-7596
VL - 17
JO - Genome Biology
JF - Genome Biology
IS - 1
M1 - 174
ER -