Distribution, phenotype and dysfunctional mechanism of CD8+ CD103+ tissue-resident memory T cells in gastric cancer patients
Objective To investigate the distribution and phenotypic features of CD8+CD103+ tissue-resident memory T cells (Trm) in gastric cancer (GC) patients, and to explore their dysfunctional mechanism. Methods The number of CD8+CD103+ Trm cells in GC tissues was detected by immunohistochemical staining and its correlation with clinical stages of GC patients was subsequently analyzed. The proportion, phenotype and function of CD8+CD103+ Trm cells in tissues of GC patients were determined using flow cytometry. In addition, CD8+ T cells were cultured with transforming growth factor-β1(TGF-β1) stimulation in vitro, and the effects of TGF-β1 on the function of CD8+CD103+ Trm cells were explored. Results The number of CD8+CD103+ Trm cells in GC tissues was not greatly altered (P<0.05), but its proportion in CD8+ T cells was significantly declined than that of normal tissues (P < 0.05). The main population of tumor-infiltrating CD8+CD103+ Trm cells belonged to the type of effector memory cells (CD45RA-CCR7-), which showed higher expression of CD69 and PD-1 while lower expression of granzyme B and perforin than CD8+CD103- T cells (P < 0.05). In vitro culture displayed that TGF-β1 induced the down-regulation of granzyme B and perforin expression in CD8+CD103+ Trm cells. Moreover, the number of tumor-infiltrating CD8+CD103+ Trm cells in advanced GC patients was found significantly decreased than that in early GC patients (P < 0.05). Conclusion The infiltration level of CD8+CD103+ Trm cells in GC tissues is negatively correlated with GC progression. These cells show an inhibitory phenotype as well as decreased anti-tumor function, thus contributing to immune escape of GC..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:43 |
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| Enthalten in: |
Di-san junyi daxue xuebao - 43(2021), 12, Seite 1146-1152 |
| Sprache: |
Chinesisch |
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| Beteiligte Personen: |
SHEN Yang [VerfasserIn] |
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| Links: |
doi.org [kostenfrei] |
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| Themen: |
Astric cancer |
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| doi: |
10.16016/j.1000-5404.202012107 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
DOAJ014487950 |
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| 520 | |a Objective To investigate the distribution and phenotypic features of CD8+CD103+ tissue-resident memory T cells (Trm) in gastric cancer (GC) patients, and to explore their dysfunctional mechanism. Methods The number of CD8+CD103+ Trm cells in GC tissues was detected by immunohistochemical staining and its correlation with clinical stages of GC patients was subsequently analyzed. The proportion, phenotype and function of CD8+CD103+ Trm cells in tissues of GC patients were determined using flow cytometry. In addition, CD8+ T cells were cultured with transforming growth factor-β1(TGF-β1) stimulation in vitro, and the effects of TGF-β1 on the function of CD8+CD103+ Trm cells were explored. Results The number of CD8+CD103+ Trm cells in GC tissues was not greatly altered (P<0.05), but its proportion in CD8+ T cells was significantly declined than that of normal tissues (P < 0.05). The main population of tumor-infiltrating CD8+CD103+ Trm cells belonged to the type of effector memory cells (CD45RA-CCR7-), which showed higher expression of CD69 and PD-1 while lower expression of granzyme B and perforin than CD8+CD103- T cells (P < 0.05). In vitro culture displayed that TGF-β1 induced the down-regulation of granzyme B and perforin expression in CD8+CD103+ Trm cells. Moreover, the number of tumor-infiltrating CD8+CD103+ Trm cells in advanced GC patients was found significantly decreased than that in early GC patients (P < 0.05). Conclusion The infiltration level of CD8+CD103+ Trm cells in GC tissues is negatively correlated with GC progression. These cells show an inhibitory phenotype as well as decreased anti-tumor function, thus contributing to immune escape of GC. | ||
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