Immune signatures predict prognosis in localized cancer.
The host immune response can impact cancer growth, prognosis, and response to therapy. In colorectal cancer, the presence of cells involved with T-cell-mediated adaptive immunity predicts survival better than the current staging method. We used the expression of genes recently associated with host immune responses (T(H1)-mediated adaptive immunity, inflammation, and immune suppression) to perform hierarchical clustering of multiple large cohorts of cancer specimens to determine if immune-related gene expression resulted in clinical significant groupings of tumors. Microarray data from prostate cancer (n = 79), breast cancer (n = 132), lung cancer (n = 84), glioblastoma multiforme (n = 120), and lymphoma (n = 127) were analyzed. Among adenocarcinomas, the T(H1)-mediated adaptive immunity genes were consistently associated with better prognosis, while genes associated with inflammation and immune suppression were variably associated with outcome. Specifically, increased expression of the T(H1)-mediated adaptive immunity genes was associated with good prognosis in breast cancer patients under 45 years of age (p = .04, hazard ratio [HR] = 0.42) and in prostate cancer patients (p = .03, HR = 0.36) but not in lung cancer patients (p = 0.45, HR = 1.37). In lymphoma, patients with increased expression of inflammation and immune suppression genes had better prognosis than those expressing the T(H1)-mediated adaptive immunity genes (p = .01, HR = 0.43) and in glioblastoma multiforme, the expression of inflammation genes conferred improved prognosis than those expressing immune suppression genes (p = 0.05, HR = 0.62). In aggregate, the gene expression signatures implicating specific components of the immune response hold prognostic import across solid tumors.
Hsu
David S
DS
Duke Institute for Genome Sciences and Policy, Department of Internal Medicine, Duke University Medical Center, Durham, North Carolina, USA.
Kim
Mickey K
MK
Balakumaran
Bala S
BS
Acharya
Chaitanya R
CR
Anders
Carey K
CK
Clay
Tim
T
Lyerly
H Kim
HK
Drake
Charles G
CG
Morse
Michael A
MA
Febbo
Phillip G
PG
D056704:Adaptive Immunity; D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology; D000328:Adult; D016000:Cluster Analysis; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007249:Inflammation / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology*; D011379:Prognosis