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Cited by 23Cancer Immunotherapy and BiomarkersT-cell and B-cell ImmunologyImmunotherapy and Immune Responses

Alterations in composition of immune cells and impairment of anti-tumor immune response in aged oral cancer-bearing mice

Sekido, Katsuhisa, Tomihara, Kei, Tachinami, Hidetake, Heshiki, Wataru, Sakurai, Kotaro, Moniruzzaman, Rohan, Imaue, Shuichi, Fujiwara, Kumiko +1 more·2019·Oral Oncology
DOI 10.1016/j.oraloncology.2019.104462
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Abstract

Objectives Aging has been suggested to be associated with immune dysregulation. An understanding of alterations in the host immunity with advancing age is, therefore, important for designing immune therapy for elderly cancer patients. In this context, not much is known about age-associated alterations in the immune system in oral cancer.Methods To evaluate age-associated alterations in the immune system, which might affect anti-tumor immune responses in oral cancer, we performed a comparative analysis of the proportion of different immune cells, the proliferative capacity of T cell compartment, and the response against immune therapies targeting immune check point molecules between young and aged oral cancer-bearing mice.Results The proportion of immune regulatory cells, such as regulatory T cells and myeloid derived suppressor cells, was significantly increased in aged mice compared to that in young mice. Moreover, the expression of PD-1 and CTLA-4 on both CD4+ and CD8+ T cells was elevated in aged mice compared to that in young mice, and the proliferative abilities of CD4+ and CD8+ T cells derived from aged mice were significantly reduced following stimulation of T-cell receptors. Moreover, tumor growth was significantly enhanced in aged mice compared to that in young mice. However, immunotherapies targeting PD-1, CTLA-4, and PD-L1 resulted in faster tumor regression in aged mice than in young mice.Conclusions Together, our results indicate that age-associated alterations in the immune system are directly associated with the impairment of anti-tumor immunity in aged mice bearing oral cancer, and might facilitate the progression of the tumor.

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  • In an oral cancer tumor-bearing mouse model, tumor regression of aged mice after anti-PD-L1 treatment was faster than that of young mice.

    “Moreover, in an oral cancer tumor-bearing mouse model, the tumor regression of aged mice after anti-PD-L1 treatment was faster than that of young mice [161].”

    From Immunosenescence: a key player in cancer development (2020) · cites this paper as [161]

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Authors
Sekido, K., Tomihara, K., Tachinami, H., Heshiki, W., Sakurai, K., Moniruzzaman, R., Imaue, S., Fujiwara, K., & Noguchi, M.
Affiliations
University of Toyama (JP)
Corresponding author
Tomihara, Kei
ORCID
Venue
Oral Oncology
Publisher
Elsevier BV
Published
2019-12
Volume
99
Pages
104462
ISSN
1368-8375 (ISSN-L)
DOI
10.1016/j.oraloncology.2019.104462
OpenAlex
W2986851958
Cited by
23
References
61
Citations by year
2026: 3 · 2025: 6 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 3
FWCI
0.94
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Oral Oncology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Japan Society for the Promotion of Science (JP19K10262, JP16K11720, KAKENHI)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
aging, oral cancer, antitumor immunity, immune dysregulation, regulatory T cells, myeloid-derived suppressor cells, PD-1, CTLA-4, PD-L1, immune checkpoint inhibitors, T cell proliferation, tumor growth, aged mice
MeSH terms
Aged, Animals, Female, Humans, Immunotherapy, Cell Line, Tumor, Cell Proliferation, Mice

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