A5041223630- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- CAR-T cell therapy research
- Chemokine receptors and signaling
- Immunotherapy and Immune Responses
- Acupuncture Treatment Research Studies
- Effects of Radiation Exposure
- Complementary and Alternative Medicine Studies
- Phagocytosis and Immune Regulation
National Institute on Deafness and Other Communication Disorders
2019-2020
National Institutes of Health
2019-2020
National Center for Tumor Diseases
2019
Indiana University Bloomington
2012
Abstract Purpose: Natural killer (NK)-cell–based immunotherapy may overcome obstacles to effective T-cell–based such as the presence of genomic alterations in IFN response genes and antigen presentation machinery. All approaches be abrogated by an immunosuppressive tumor microenvironment present many solid types, including head neck squamous cell carcinoma (HNSCC). Here, we studied role myeloid-derived suppressor cells (MDSC) suppressing NK-cell function HNSCC. Experimental Design: The...
Recruitment of myeloid-derived suppressor cells (MDSCs) into tumors induces local immunosuppression in carcinomas. Here, we assessed whether SX-682, an orally bioavailable small-molecule inhibitor CXCR1 and CXCR2, could block tumor MDSC recruitment enhance T cell activation antitumor immunity following multiple forms immunotherapy. CXCR2+ neutrophilic MDSCs (PMN-MDSCs) were the most abundant myeloid subset within oral lung syngeneic PMN-MDSCs demonstrated greater suppression...
Surgical resection of primary tumor with regional lymphadenectomy remains the treatment choice for patients advanced human papillomavirus-negative head and neck squamous cell carcinoma. However, even when pathologic disease-free margins can be achieved, locoregional and/or distant disease relapse high. Perioperative immunotherapy may improve outcomes, but mechanistic data supporting use neoadjuvant or adjuvant clinically are sparse.Two syngeneic models oral cavity carcinoma defined T-cell...
Failed T cell-based immunotherapies in the presence of genomic alterations antigen presentations pathways may be overcome by NK immunotherapy. This approach still limited immunosuppressive myeloid populations. Here, we demonstrate that cells (haNKs) engineered to express a PD-L1 chimeric receptor (CAR) haNKs killed panel human and murine head neck cancer at low effector-to-target ratios PD-L1-dependent fashion. Treatment syngeneic tumors resulted CD8 tumor rejection or growth inhibition...
Abstract Failed T cell-based immunotherapies in the presence of genomic alterations antigen presentations pathways may be overcome by NK immunotherapy. This approach still limited immunosuppressive myeloid populations. Here we demonstrate that cells (haNKs) engineered to express a PD-L1 chimeric receptor (CAR) haNKs killed panel human and murine head neck cancer at low effector-to-target ratios PD-L1-dependent fashion. Treatment syngeneic tumors resulted CD8 tumor rejection or growth...
<p>Supplemental data not critical for the main conclusions of work but important review data.</p>
<p>Supplemental Figure S1. MOC2 tumors express myeloid chemokines</p>
<p>Supplemental Figure S2. PMN-MDSC can be isolated from tumor single cell suspensions</p>
<p>Methods not essential to the main conclusions but important for critical review of methods used this work</p>
<p>Supplemental Figure S3. Tumor PMN-MDSC do not inhibit KIL effector function through PD-L1, arginase or NOS</p>
<p>Supplemental Figure S7. SX-682 treatment does not alter PMN-MDSC suppressive capacity</p>
<p>Supplemental Figure S4. Ex vivo SX-682 exposure does not reduce the viability of sorted MDSC</p>
<p>Supplemental Figure S8. SX-682 does not directly alter MOC2 cells in vitro</p>
<p>Supplemental Figure S5. SX-682 treatment does not alter the proliferation of PMN-MDSC within MOC2 tumors.</p>
<p>Supplemental Figure S6. SX-682 treatment does not enhance MOC2 tumor T cell infiltration</p>
<p>Supplemental data not critical for the main conclusions of work but important review data.</p>
<p>Supplemental Figure S1. MOC2 tumors express myeloid chemokines</p>
<p>Methods not essential to the main conclusions but important for critical review of methods used this work</p>
<p>Supplemental Figure S5. SX-682 treatment does not alter the proliferation of PMN-MDSC within MOC2 tumors.</p>
<p>Supplemental Figure S4. Ex vivo SX-682 exposure does not reduce the viability of sorted MDSC</p>
<p>Supplemental Figure S6. SX-682 treatment does not enhance MOC2 tumor T cell infiltration</p>
<p>Supplemental Figure S2. PMN-MDSC can be isolated from tumor single cell suspensions</p>
<p>Supplemental Figure S8. SX-682 does not directly alter MOC2 cells in vitro</p>