Supplementation of l‐arginine boosts the therapeutic efficacy of anticancer chemoimmunotherapy

Autor: Yuichi Iida, Mamoru Harada, Hitoshi Kotani, Yusuke Satoh, Takahito Taniura, Yoshitomo Notsu
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Cancer Research
Arginine
medicine.medical_treatment
MDSC
l‐arginine
Pharmacology
CD8-Positive T-Lymphocytes
Mice
0302 clinical medicine
Basic and Clinical Immunology
Antineoplastic Agents
Immunological
T-Lymphocyte Subsets
Neoplasms
Medicine
Amino Acids
biology
Immunosuppression
Drug Synergism
General Medicine
Flow Cytometry
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
chemoimmunotherapy
Original Article
Female
Lymph
Antibody
medicine.drug
Cyclophosphamide
T cells
Spleen
Antineoplastic Agents
arginase-I
arginase‐I
03 medical and health sciences
Chemoimmunotherapy
Cell Line
Tumor
Animals
l-arginine
Cell Proliferation
Dose-Response Relationship
Drug
business.industry
Myeloid-Derived Suppressor Cells
Original Articles
030104 developmental biology
Dietary Supplements
biology.protein
business
CD8
Zdroj: Cancer Science
ISSN: 1349-7006
1347-9032
Popis: Myeloid‐derived suppressor cells (MDSCs) play a crucial role in immunosuppression in tumor‐bearing hosts. MDSCs express arginase‐I and indoleamine 2,3‐dioxygenase; they suppress T‐cell function by reducing the levels of l‐arginine and l‐tryptophan, respectively. We examined the anticancer effects of supplementation of these amino acids in CT26 colon carcinoma‐bearing mice. Oral supplementation of l‐arginine or l‐tryptophan (30 mg/mouse) did not affect tumor growth, whereas oral supplementation of d‐arginine was lethal. Supplementation of l‐arginine showed a tendency to augment the efficacy of cyclophosphamide (CP). CP reduced the proportions of granulocytic MDSCs and increased the proportions of monocytic MDSCs in the spleen and tumor tissues of CT26‐bearing mice. l‐Arginine supplementation alone did not affect the MDSC subsets. CP treatment tended to reduce the plasma levels of l‐arginine in CT26‐bearing mice and significantly increased the number of tumor‐infiltrating CD8+ T cells. In addition, l‐arginine supplementation significantly increased the proportions of tumor peptide‐specific CD8+ T cells in draining lymph nodes. Importantly, additional supplementation of l‐arginine significantly increased the number of cured mice that were treated with CP and anti‐PD‐1 antibody. Totally, l‐arginine supplementation shows promise for boosting the therapeutic efficacy of chemoimmunotherapy.
Combination treatment with cyclophosphamide and anti‐PD‐1 antibody significantly suppressed the tumor growth, but did not exert a curative effect. However, the addition of l‐arginine supplementation boosted to complete regression in the majority of mice.
Databáze: OpenAIRE
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