isolation-of-immune-cells-from-primary-tumors

Isolation of Immune Cells from Primary Tumors

Tumors create a unique immunosuppressive microenvironment (tumor microenvironment, TME) whereby leukocytes are recruited into the tumor by various ...

National Cancer Institute - Frederick

This study reveals that the IL-15 rapidly released into serum upon IL-12 injection into tumor-bearing mice is critical for the subsequent leukocytic infiltration of the tumor and tumor-bearing tissue. The increase in serum IL-15 occurs within 2 h after IL-12 injection concomitantly with a decrease in cytoplasmic IL-15 in tumor-associated Mphi (TAM). Injection of anti-IL-15 one hour prior to IL-12 abrogates subsequent leukocytic infiltration into the tumor and prevents the IL-12-induced reduction of primary tumor mass and the clearance of metastases. Administration of anti-IL-15 18 h after IL-12 did not have a detectable impact on IL-12-induced leukocytic infiltration of the tumor. Deletion of NK cells had no impact on the IL-12-induced change in the functional phenotype of TAM or on the subsequent initiation of leukocytic infiltration of the tumor. In concert with our previous studies demonstrating that IL-12 reduces tumor-supportive activities of TAM, the current study supports the hypothesis that functional re-programming of TAM not only undermines Mphi support for tumor growth but also contributes to a critical step in the initiation of anti-tumor immune responses. In this context, the functional plasticity and pro-immunogenic potential of TAM may constitute a significant and unappreciated target in existing cytokine therapies.

Article	Year
Journal of immunology (Baltimore, Md. : 1950)\| PubMed ID: 15972667	2005
Journal of immunology (Baltimore, Md. : 1950)\| PubMed ID: 17237382	2007
Journal of leukocyte biology\| PubMed ID: 19605698	2009
Rapid release of cytoplasmic IL-15 from tumor-associated macrophages is an initial and critical event in IL-12-initiated tumor regression. European journal of immunology\| PubMed ID: 19609975	2009
Cancer research\| PubMed ID: 19622771	2009
The Journal of clinical investigation\| PubMed ID: 21436588	2011
Nucleic acids research\| PubMed ID: 22210864	2012
Cancer immunology, immunotherapy : CII\| PubMed ID: 22237887	2012

Stephanie K. Watkins

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