Neem leaf glycoprotein generates superior tumor specific central memory CD8+ T cells than cyclophosphamide that averts post-surgery solid sarcoma recurrence.
Vaccine
; 35(34): 4421-4429, 2017 08 03.
Article
em En
| MEDLINE
| ID: mdl-28684164
ABSTRACT
The success of cancer vaccines is limited as most of them induce corrupted CD8+ T cell memory populations. We reported earlier that a natural immunomodulator, neem leaf glycoprotein (NLGP), therapeutically restricts tumor growth in a CD8+ T cell-dependent manner. Here, our objective is to study whether memory CD8+ T cell population is generated in sarcoma hosts after therapeutic NLGP treatment and their role in prevention of post-surgery tumor recurrence, in comparison to the immunostimulatory metronomic cyclophosphamide (CTX) treatment. We found that therapeutic NLGP and CTX treatment generates central memory CD8+ T (TCM) cells with characteristic CD44+CD62LhighCCR7highIL-2high phenotypes. But these TCM cells are functionally impaired to prevent re-appearance of tumors along with compromised proliferative, IL-2 secretive and cytotoxic status. This might be due to the presence of tumor load, even a small one in the host, which serves as a persistent source of tumor antigens thereby corrupting the TCM cells so generated. Surgical removal of the persisting tumors from the host restored the functional characteristics of memory CD8+ T cells, preventing tumor recurrence after surgery till end of the experiment. Moreover, we observed that generation of superior TCM cells in NLGP treated surgically removed tumor hosts is related to the activation of Wnt signalling in memory CD8+ T cells with concomitant inhibition of GSK-3ß and stabilisation of ß-catenin, which ultimately activates transcription of Wnt target genes, like, eomesodermin, a signature molecule of CD8+ TCM cells.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
1_ASSA2030
Problema de saúde:
1_doencas_nao_transmissiveis
Assunto principal:
Sarcoma
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Extratos Vegetais
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Glicoproteínas
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Linfócitos T CD8-Positivos
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Azadirachta
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Memória Imunológica
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Recidiva Local de Neoplasia
Limite:
Animals
Idioma:
En
Revista:
Vaccine
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Índia