Intratumoral rhIL-12 administration in head and neck squamous cell carcinoma patients induces B cell activation

Autor: Robbert van der Voort, Gosse J. Adema, I. Jolanda M. de Vries, Ina S. Klasen, Aniek O. de Graaf, Tjitske Duiveman-de Boer, Jeroen van der Laak, Ruurd Torensma, Johan H. J. M. van Krieken, Léon C van Kempen, Harry Dolstra, Carla M.L. van Herpen, Pieter H.M. De Mulder
Rok vydání: 2008
Předmět:
Male
Cancer Research
Pathology
Genetics and epigenetic pathways of disease [NCMLS 6]
medicine.medical_treatment
Injections
Intralesional
Lymphocyte Activation
Polymerase Chain Reaction
Immunophenotyping
Immune Regulation [NCMLS 2]
Molecular diagnosis
prognosis and monitoring [UMCN 1.2]
Chronic inflammation and autoimmunity [UMCN 4.2]
B-Lymphocytes
Middle Aged
Immunohistochemistry
Interleukin-12
Recombinant Proteins
Pathogenesis and modulation of inflammation [N4i 1]
Cytokine
medicine.anatomical_structure
Oncology
Head and Neck Neoplasms
Carcinoma
Squamous Cell
Female
Lymph
medicine.medical_specialty
Age-related aspects of cancer [ONCOL 2]
Interferon-gamma
Translational research [ONCOL 3]
Carcinoma
medicine
Humans
RNA
Messenger
B cell
Aged
DNA Primers
Hereditary cancer and cancer-related syndromes [ONCOL 1]
Base Sequence
business.industry
Tumor-infiltrating lymphocytes
Germinal center
Immunotherapy
gene therapy and transplantation [UMCN 1.4]
Tissue engineering and pathology [NCMLS 3]
medicine.disease
Head and neck squamous-cell carcinoma
Tumor microenvironment [UMCN 1.3]
Lymph Nodes
business
Immunity
infection and tissue repair [NCMLS 1]
Zdroj: International Journal of Cancer, 123, 10, pp. 2354-61
International Journal of Cancer, 123, 2354-61
ISSN: 0020-7136
Popis: Contains fulltext : 69631.pdf (Publisher’s version ) (Open Access) 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-gamma 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.
Databáze: OpenAIRE
Externí odkaz: