Abstract | 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.
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Authors | Theresa L Whiteside, Lisa H Butterfield, Paul H Naylor, James E Egan, John W Hadden, Lorraine Baltzer, Gregory T Wolf, Neil L Berinstein |
Journal | Cancer immunology, immunotherapy : CII
(Cancer Immunol Immunother)
Vol. 61
Issue 6
Pg. 783-8
(Jun 2012)
ISSN: 1432-0851 [Electronic] Germany |
PMID | 22109700
(Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- 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)
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