Document Detail


A short course of neoadjuvant IRX-2 induces changes in peripheral blood lymphocyte subsets of patients with head and neck squamous cell carcinoma.
MedLine Citation:
PMID:  22109700     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: IRX-2, a primary cell-derived biologic with pleotropic immune activity, was shown to induce increased lymphocyte infiltrations into the tumor of patients with head and neck squamous cell cancer (HNSCC) after 10 days of neoadjuvant therapy (Berinstein et al. 2011). In the same patients enrolled in the Phase II study, peripheral blood lymphocyte subsets were monitored pre- and post-IRX-2 therapy to evaluate changes induced by IRX-2.
METHODS: Absolute lymphocyte numbers were determined in whole blood using the TetraONE System. Lymphocytes were further separated on Ficoll-Hypaque gradients and evaluated by multiparameter flow cytometry. Lymphocyte numbers, including regulatory T cells (Treg) and naïve, memory and effector T cells, were compared in pre- and post-therapy specimens.
RESULTS: Total lymphocyte numbers remained unchanged after IRX-2 therapy. Significant changes occurred in numbers of circulating B cells and NKT cells, which decreased following IRX-2 therapy. The frequency of circulating Treg (CD4(+)CD25(high)) remained unaltered (e.g., 6.7 ± 0.6% vs. 7.5 ± 0.8%; means ± SEM) as was the CD8(+)/Treg ratio (6.6 before and 6.7 after IRX-2 therapy). The mean absolute number of CD3(+)CD45RA(+)CCR7(+) (naïve) T cells was decreased after IRX-2 therapy but numbers of total memory (i.e., central and peripheral) and terminally differentiated T cells were unchanged.
CONCLUSIONS: IRX-2-mediated reductions in B and NKT cell numbers in the blood suggest a redistribution of these cells to tissues. A decrease in naïve T cells implies their up-regulated differentiation to memory T cells. Unchanged Treg numbers after IRX-2 therapy indicate that IRX-2 does not expand this compartment, potentially benefiting anti-tumor immune responses.
Authors:
Theresa L Whiteside; Lisa H Butterfield; Paul H Naylor; James E Egan; John W Hadden; Lorraine Baltzer; Gregory T Wolf; Neil L Berinstein
Publication Detail:
Type:  Clinical Trial, Phase II; Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-11-23
Journal Detail:
Title:  Cancer immunology, immunotherapy : CII     Volume:  61     ISSN:  1432-0851     ISO Abbreviation:  Cancer Immunol. Immunother.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-05-30     Completed Date:  2012-08-20     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  8605732     Medline TA:  Cancer Immunol Immunother     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  783-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Carcinoma, Squamous Cell / diagnosis,  immunology,  therapy*
Cytokines / administration & dosage,  immunology,  pharmacology,  therapeutic use*
Head and Neck Neoplasms / diagnosis,  immunology,  therapy*
Humans
Lymphocytes, Tumor-Infiltrating / immunology,  pathology
Neoadjuvant Therapy*
T-Lymphocyte Subsets / drug effects*,  immunology,  pathology
Grant Support
ID/Acronym/Agency:
P01 CA109688/CA/NCI NIH HHS; P01-CA109688/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Cytokines; 0/IRX 2
Comments/Corrections

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