CpG-ODN but not other TLR-ligands restore the antitumor responses in old mice: the implications for vaccinations in the aged
Open accessAbstract
Aim There is accumulative evidence indicating that targeting antigen presenting cells (APCs) with different types of adjuvants could result in the induction of antitumor immune responses. It has been hypothesized that APCs function may be altered in the elderly contributing to a decline in the immune function. We evaluated whether targeting APCs following injection with Poly I:C, LPS, flagellin, imiquimod and CpG-ODN would induce an antitumor response in the old.Materials and methods The immune and antitumor responses induce Poly I:C, LPS, flagellin, imiquimod and CpG-ODN were compared in young (2 month old) and old (18 months) mice.Results Our results indicated that only intratumoral (i.t.) injections of CpG-ODN completely rejected the tumor in both young and old mice. Injections of Poly I:C also induced the rejection of tumors in the young but not in the old. Furthermore, i.t. injections of CpG-ODN promoted the development of protective memory responses in the young and the old. Analysis of the immune responses in the old indicated that CpG-ODN but not Poly-I:C induces: a pro-inflammatory Th1 type response; accumulation and activation of CD4+, CD8+ T and, NK cell responses; activation of APCs; and reduction in the number of Tregs. The activation of these immune-parameters positively correlates with the induction of an antitumor response.Conclusions These studies indicate that there are differences in the level of stimulation with TLR-ligands between young and old APCs and that the aged immune responses can be rescued and exploited for the induction of tumor immunity by targeting APCs with specific TLR-ligands. These results have important clinical implications for developing immunization strategies containing TLR-ligands that will be effective in both the young and old.
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The addition of PAMPs to a subunit vaccine, triggering their corresponding pattern-recognition receptors (e.g., TLRs), improves vaccine efficacy in older humans and mice.
“On the other hand, the addition of PAMPs to a subunit vaccine, triggering their corresponding pattern-recognition receptors (e.g., TLRs) improves vaccine efficacy in older humans and mice (25, 30–32).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [32]
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- Authors
- Sharma, S., Dominguez, A. L., Hoelzinger, D. B., & Lustgarten, J.
- Affiliations
- Mayo Clinic in Arizona (US)
- Corresponding author
- Lustgarten, Joseph
- Venue
- Cancer Immunology Immunotherapy
- Published
- 2007-09-08
- Volume
- 57
- Issue
- 4
- Pages
- 549-561
- ISSN
- 0340-7004 (ISSN-L)
- 1432-0851
- PMC
- PMC11031019
- OpenAlex
- W2062137566
- Cited by
- 46
- References
- 42
- Citations by year
- 2025: 3 · 2023: 1 · 2021: 1 · 2020: 1 · 2019: 4 · 2018: 1 · 2017: 2 · 2016: 3 · 2015: 2 · 2013: 2 · 2012: 2
- FWCI
- 2.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cancer Immunology Immunotherapy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG028751, R01AG028751)
- National Cancer Institute (CA78579, R01CA078579)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- CpG oligodeoxynucleotides, TLR ligands, immunosenescence, aged mice, antitumor immunity, antigen-presenting cells, poly(I:C), LPS, flagellin, imiquimod, intratumoral injection, tumor rejection, memory T cells, Th1 response, regulatory T cells, natural killer cells, adjuvants
- MeSH terms
- Imiquimod, Adjuvants, Immunologic, Aging, Aminoquinolines, Animals, Antigen-Presenting Cells, Flagellin, Flow Cytometry, Ligands, Lipopolysaccharides, Mammary Neoplasms, Experimental, Mice, Inbred BALB C, Mice, Inbred C57BL, Oligodeoxyribonucleotides, Poly I-C, T-Lymphocytes, Vaccination, Cytokines, Toll-Like Receptors, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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