Intratumoral rhIL‐12 administration in head and neck squamous cell carcinoma patients induces B cell activation
- 12 September 2008
- journal article
- clinical trial
- Published by Wiley in International Journal of Cancer
- Vol. 123 (10), 2354-2361
- https://doi.org/10.1002/ijc.23756
Abstract
The objectives of this study were to investigate the effects of intratumorally (i.t.) administered recombinant human interleukin‐12 (rhIL‐12) on the distribution and function of B cells in the primary tumors, the locoregional lymph nodes and peripheral blood of head and neck squamous cell carcinoma (HNSCC) patients. The initial characterization of the patients participating in the phase Ib and phase II studies has previously been reported. After rhIL‐12 treatment, fewer secondary follicles with a broader outer region of the mantle zones and an increase in interfollicular B‐blasts were seen in the enlarged lymph nodes compared with control HNSCC patients. The size of the germinal center (GC) was diminished, partly due to a decrease in the number of CD57+ GC cells that have been associated with immune suppression. These changes did not correlate with signs of apoptosis or CXCR5 expression by B cells. Strikingly, in 3 out of 4 IL‐12 treated patients, increased IFN‐γ mRNA expression by B cells was detected. In addition, a highly significant IgG subclass switch was seen in the plasma with more IgG1, less IgG2 and more IgG4, indicating a switch to T helper 1 phenotype. Finally, peritumoral B cell infiltration was a positive prognostic sign for overall survival in the 30 HNSCC patients investigated, irrespective of IL‐12 treatment. In conclusion, these data indicate that after i.t. IL‐12 treatment in HNSCC, significant activation of the B cell and the B cell compartment occurred and that the presence of tumor infiltrating B cells correlated with overall survival of HNSCC patients.Keywords
This publication has 34 references indexed in Scilit:
- Intratumoral Recombinant Human Interleukin-12 Administration in Head and Neck Squamous Cell Carcinoma Patients Modifies Locoregional Lymph Node Architecture and Induces Natural Killer Cell Infiltration in the Primary TumorClinical Cancer Research, 2005
- In human B cells, IL-12 triggers a cascade of molecular events similar to Th1 commitmentBlood, 2003
- Interleukin-12 and the regulation of innate resistance and adaptive immunityNature Reviews Immunology, 2003
- Evaluation of Recombinant Human Interleukin-12 in Patients with Recurrent or Refractory Ovarian Cancer: A Gynecologic Oncology Group StudyGynecologic Oncology, 2001
- Randomized Multicenter Phase II Trial of Subcutaneous Recombinant Human Interleukin-12 Versus Interferon-α2a for Patients with Advanced Renal Cell CarcinomaJournal of Interferon & Cytokine Research, 2001
- Systemic administration of rIL-12 induces complete tumor regression and protective immunity: response is correlated with a striking reversal of suppressed IFN-γ production by anti-tumor T cellsInternational Immunology, 1995
- Interleukin-10 prevents spontaneous death of germinal center B cells by induction of the bcl-2 protein.JCI Insight, 1994
- Antitumor and antimetastatic activity of interleukin 12 against murine tumors.The Journal of Experimental Medicine, 1993
- Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes.The Journal of Experimental Medicine, 1989
- Nonparametric Estimation from Incomplete ObservationsJournal of the American Statistical Association, 1958