Th1/Th2 cytokine expression and its relationship with tumor growth in B cell non-Hodgkin's lymphoma (NHL).
AT helper 1 (Th1) immune response is considered more effective than T helper 2 (Th2) for anti-tumor immunity, but either response could potentially stimulate tumor cell growth in lymphomas. Moreover, both IL-4 and IL-2/IL-12 are used in experimental treatment models for non-Hodgkin's lymphoma (NHL) despite their differing ability to elicit Th2 or Th1 responses, respectively. Here, we investigate which T helper cytokines (Th1 or Th2) predominate in B cell NHL tissue and determine whether cytokine expression correlates with tumor cell growth, cell death, and survival in a series of 44 NHL patients. Overall, we observed both Th1 and Th2 cytokine expression at the mRNA level, detecting high levels of IFN-gamma, IL6 and IL-10 expression in the majority of tumors. Transcripts for the IL-12 subunits p35 (38 of 38) and p 40 (23 of 38) were frequently detected in NHL tissue, and high p40 levels were common in patients with a good prognosis. Furthermore, high IL-4 levels correlated with greater survival duration (P < 0.0024) but nor overall survival. Cytokine expression of IL-2, IFNgamma and IL-4 was significantly reduced in the high grade tumor group. Interestingly, there was a strong correlation between high IL-4 levels and reduced levels of apoptosis (P < 0.006) or proliferation (P < 0.0001), which has also been reported in leukemic models. This has important implications for the success of IL-4 as a treatment for low and high grade tumors.
Jones
E A
EA
Institute for Cancer Studies, University of Sheffield Medical School, UK. eajones30@yahoo.com
Pringle
J H
JH
Angel
C A
CA
Rees
R C
RC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D017209:Apoptosis; D002455:Cell Division; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics; D053762:Interleukin-12 Subunit p40; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D021122:Protein Subunits / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*; D014750:Vincristine / Q000008:administration & dosage
D016207:Cytokines; D053762:Interleukin-12 Subunit p40; D021122:Protein Subunits; D018664:Interleukin-12; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone