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A short course of neoadjuvant IRX-2 induces changes in peripheral blood lymphocyte subsets of patients with head and neck squamous cell carcinoma

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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+CD25high) 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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Notes

  1. Berinstein et al. [26].

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Acknowledgments

Financial Support: Supported in part by a grant from NIH (PO1-CA109688) and by IRX Therapeutics Inc.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Research Pavilion at the Hillman Cancer Center, University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Suite 1.27, Pittsburgh, PA, 15213-1863, USA

    Theresa L. Whiteside & Lisa H. Butterfield

  2. IRX Therapeutics Inc, New York, NY, USA

    Paul H. Naylor, James E. Egan, John W. Hadden, Lorraine Baltzer & Neil L. Berinstein

  3. University of Michigan, Ann Arbor, MI, USA

    Gregory T. Wolf

Authors
  1. Theresa L. Whiteside
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  2. Lisa H. Butterfield
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  3. Paul H. Naylor
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  5. John W. Hadden
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  6. Lorraine Baltzer
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  7. Gregory T. Wolf
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  8. Neil L. Berinstein
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Correspondence to Theresa L. Whiteside.

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Whiteside, T.L., Butterfield, L.H., Naylor, P.H. et al. A short course of neoadjuvant IRX-2 induces changes in peripheral blood lymphocyte subsets of patients with head and neck squamous cell carcinoma. Cancer Immunol Immunother 61, 783–788 (2012). https://doi.org/10.1007/s00262-011-1136-x

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  • DOI: https://doi.org/10.1007/s00262-011-1136-x

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