Oncogene and cytokine expression of human colorectal tumors responding to immunotherapy.
Tumor samples from five patients with metastatic colorectal cancer who demonstrated tumor regressions in clinical trials of interleukin (IL)-1 beta, IL-2, and adoptive cellular therapy were analyzed for oncogene and cytokine mRNA expression. Tumors from eight nonresponding patients were also studied. Mutations of the ras protooncogene and overexpression of c-myc protooncogene were observed in both responding and nonresponding tumors. In contrast, none of the responding tumors expressed transforming growth factor (TGF)-beta 1 mRNA, whereas nonresponding tumors did. The expression of IL-1, IL-6, IL-8, IL-10, tumor necrosis factor-alpha, granulocyte macrophage-colony-stimulating factor, macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, macrophage chemotactic protein, and RANTES was variable between responding and nonresponding patients. Although we cannot conclude that a pattern of oncogene and/or cytokine mRNA expression specifically characterizes sensitive colorectal cancers, these analyses-the assessment of TGF-beta 1 mRNA in particular-merit further evaluation as biomarkers prognostic of immunotherapy response.
Doran
T
T
Ohio State University Arthur G. James Cancer Hospital and Research Institute, Columbus, USA.
Stuhlmiller
H
H
Kim
J A
JA
Martin
E W
EW
Triozzi
P L
PL
D015179:Colorectal Neoplasms / Q000235:genetics* / Q000628:therapy; D016259:Genes, myc / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D007375:Interleukin-1 / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use; D009154:Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics
D007375:Interleukin-1; D007376:Interleukin-2; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta