This study was supported by Nature Science Foundation of Shandong Province (Grant Number: ZR2010HL038). Science and Technology Development Projects of Jining City (Grant Number: 2012jnjc16). None. “
“Lymphodeleption prior to adoptive transfer of tumor-specific T cells greatly improves the clinical efficacy of adoptive T-cell therapy for patients with advanced melanoma, and increases the therapeutic efficacy of cancer vaccines in animal models. Lymphodepletion reduces competition between lymphocytes, and thus creates 17-AAG price “space” for enhanced expansion and survival of tumor-specific T cells. Within the lymphodepleted host, Ag-specific T cells still need to compete

with other lymphocytes that undergo lymphopenia-driven proliferation. Herein, we describe the relative capacity of naïve T cells, Treg, and NK cells to undergo lymphopenia-driven proliferation. We found that the major population that underwent lymphopenia-driven proliferation was the CD122+ memory-like T-cell population (CD122+CD8+ Treg), and these buy RG-7388 cells competed with Ag-driven proliferation of melanoma-specific T cells. Removal of CD122+CD8+ Treg resulted in a greater expansion of tumor-specific T cells and tumor infiltration of functional effector/memory T cells. Our results demonstrate the lymphopenia-driven proliferation of CD122+CD8+ Treg in reconstituted lymphodepleted

mice limited the antitumor efficacy of DC vaccination in conjunction with adoptive transfer of tumor-specific T cells. Due in large part to the limited expansion and survival of vaccine-induced tumor Ag-specific T cells, active specific immunotherapy of tumor-bearing hosts with tumor vaccines has generally been ineffective

1. Therefore, a major goal of current T-cell based immunotherapy protocols is to induce a large number of tumor-specific T cells capable of mediating regression of established tumors and maintaining long-term memory to prevent tumor recurrence. Lymphodepletion has been recently demonstrated to facilitate the expansion and survival of therapeutic, adoptively SPTLC1 transferred in vitro-expanded T cells, which induced tumor regression in patients with melanoma (see review in 2). Concurrently, we and others have demonstrated that vaccination induced a dramatic expansion of tumor-specific T cells, and improved the efficacy of active immunotherapy in reconstituted lymphodepleted mice 3–7. While lymphopenic conditioning has been shown to benefit antitumor immunity, and aids in the establishment of the T-cell repertoire in neonatal mice 8, it was detrimental for transplant tolerance 9, and precipitated the development of autoimmune disease 10. Homeostatic proliferation, or more precisely, lymphopenia-driven proliferation of lymphocytes in irradiated or lymphocyte-deficient mice, is a well-studied phenomenon (see review 11).