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Combination Immunotherapy With LIGHT and Interleukin-2 Increases CD8 Central Memory T-Cells In Vivo.
- Source :
-
The Journal of surgical research [J Surg Res] 2021 Jul; Vol. 263, pp. 44-52. Date of Electronic Publication: 2021 Feb 22. - Publication Year :
- 2021
-
Abstract
- Background: 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 antitumor immune responses and hypothesize that combination immunotherapy may increase the CD8+ central memory T-cell response.<br />Methods: Murine colorectal cancer tumors were established in syngeneic mice. Tumors were treated with control, soluble, or liposomal 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.<br />Results: Tumors exposed to a combination of LIGHT and IL-2 experienced a decrease in tumor size compared with IL-2 alone that was not demonstrated in wild-type tumors or between other treatment groups. Combination exposure also increased splenic central memory CD8+ cells compared with 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.<br />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 antitumor responses and warrant further investigation.<br /> (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
CD8-Positive T-Lymphocytes drug effects
Cell Line, Tumor transplantation
Colonic Neoplasms genetics
Colonic Neoplasms immunology
Colonic Neoplasms pathology
Disease Models, Animal
Female
Gene Expression Regulation, Neoplastic immunology
Humans
Immunologic Memory drug effects
Injections, Intralesional
Liposomes
Lymphocytes, Tumor-Infiltrating immunology
Mice
Recombinant Proteins administration & dosage
Tumor Microenvironment genetics
Tumor Microenvironment immunology
CD8-Positive T-Lymphocytes immunology
Colonic Neoplasms therapy
Immunotherapy methods
Interleukin-2 administration & dosage
Tumor Necrosis Factor Ligand Superfamily Member 14 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1095-8673
- Volume :
- 263
- Database :
- MEDLINE
- Journal :
- The Journal of surgical research
- Publication Type :
- Academic Journal
- Accession number :
- 33631377
- Full Text :
- https://doi.org/10.1016/j.jss.2021.01.010