Combination Immunotherapy With LIGHT and Interleukin-2 Increases CD8 Central Memory T-Cells In Vivo
| Autor: | Ajay V. Maker, Bellur S. Prabhakar, Guilin Qiao, Kiara A. Tulla, Manuel Fernandez |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Interleukin 2
Tumor Necrosis Factor Ligand Superfamily Member 14 medicine.medical_treatment Spleen CD8-Positive T-Lymphocytes Injections Intralesional Article Flow cytometry Mice 03 medical and health sciences Lymphocytes Tumor-Infiltrating 0302 clinical medicine Immune system In vivo Cell Line Tumor Tumor Microenvironment Animals Humans Medicine medicine.diagnostic_test business.industry Immunotherapy Recombinant Proteins Gene Expression Regulation Neoplastic Disease Models Animal medicine.anatomical_structure 030220 oncology & carcinogenesis Colonic Neoplasms Liposomes Cancer research Interleukin-2 Female 030211 gastroenterology & hepatology Surgery Tumor necrosis factor alpha business Immunologic Memory CD8 medicine.drug |
| Zdroj: | J Surg Res |
| ISSN: | 0022-4804 |
| DOI: | 10.1016/j.jss.2021.01.010 |
| Popis: | INTRODUCTION: The generation of long-term durable tumor immunity and prolonged disease-free survival depends on the ability to generate and support CD8+ central memory T-cells. Microsatellite-stable colon cancer is resistant to currently available immunotherapies, thus, development of novel mechanisms to increase both lymphocyte infiltration and central memory formation are needed to improve outcomes in these patients. We have previously demonstrated that both Interleukin-2 (IL-2) and LIGHT (TNFSF14) independently enhance anti-tumor immune responses, and hypothesize that combination immunotherapy may increase the CD8+ central memory T-cell response. METHODS: CT26 murine colorectal cancer tumors were established in syngeneic mice. Tumors were treated with control, soluble, or liposomal Interleukin-2 (IL-2) at established intervals. A subset of animal tumors overexpressed tumor necrosis superfamily factor LIGHT (TNFSF14). Peripheral blood, splenic, and tumor infiltrating lymphocytes were isolated for phenotypic studies and flow cytometry. RESULTS: Tumors exposed to a combination of LIGHT and IL-2 experienced a decrease in tumor size compared to IL-2 alone that was not demonstrated in wild-type (wt) tumors or between other treatment groups. Combination exposure also increased splenic central memory CD8+ cells compared to IL-2 administration alone, while not increasing tumor-infiltrating lymphocytes. In the periphery, the combination enhanced levels of circulating CD8 T-cells and central memory T-cells, while also increasing circulating T-regulatory cells. CONCLUSIONS: Combination of IL-2, whether soluble or liposomal, with exposure to LIGHT results in increased CD8+ central memory cells in the spleen and periphery. New combination immunotherapy strategies that support both effector and memory T-cell functions are critical to enhancing durable anti-tumor responses and warrant further investigation. |
| Databáze: | OpenAIRE |
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