Senescence and Aging: Does It Impact Cancer Immunotherapies?

Maggiorani, Damien; Beauséjour, Christian

doi:10.3390/cells10071568

Cited by 13 publications

(6 citation statements)

References 167 publications

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“…Indeed, decrease immune functions in aged mice was reported to be associated with a decline in ICB efficacy [57][58][59]. This is in contrast to studies in humans who did not show a correlation between decrease ICB efficacy and aging [60]. For example, no decrease in the efficacy of ICB was observed in aged (over 70 years old) lung cancer patients [61].…”

Section: Discussionmentioning

confidence: 96%

Therapy-induced senescence drives immunotherapy resistance by inducing an immunosuppressive tumor microenvironment

Beauséjour

Maggiorani

Lê

et al. 2023

Preprint

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Immune checkpoint inhibitors (ICI) invigorate immune cell functions and are effective against many cancer types. However, the potential of ICI may be limited in situations where immune cell fitness is impaired. Here, we show that the efficacy of αPD-L1-based cancer immunotherapies is compromised by the accumulation of senescent cells in mice previously exposed to sublethal irradiation or injected with doxorubicin. Similarly, we observed that the efficacy of the combination of a αCTLA-4 antibody with radiotherapy is diminished in previously irradiated mice. In both models, resistance to immunotherapy was associated with a decrease in the accumulation and activation of CD8 T cells within tumors. Elimination of senescent cells by the injection of the senolytic drug ABT263, weeks before treatments, restored immune homeostasis within the tumor micro-environment (TME) and increased mice survival in both models. Using single-cell transcriptomic analysis, we observed that the injection of ABT263 reverses the exacerbated immunosuppressive profile of myeloid cells in the TME of previously irradiated mice. These myeloid cells, when purified from established tumors, were responsible for impaired CD8 T cell proliferation in vitro. Our study shows that cancer therapies, by inducing senescence, favor the formation of an immunosuppressive TME, which can alter the efficacy of ICI. The use of senolytic drugs before ICI may constitute an interesting pharmacological approach to improve the effectiveness of cancer immunotherapies.

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Section: Discussionmentioning

confidence: 96%

Therapy-induced senescence drives immunotherapy resistance by inducing an immunosuppressive tumor microenvironment

Beauséjour

Maggiorani

Lê

et al. 2023

Preprint

Self Cite

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“…Aging not only regulates cell proliferation, but also alters the TIME through the secretion of SASP, which contains MMP, growth factors (VEGF and GM-CSF), inflammatory factors (IL-6 and IL-8), and the accumulation of lipofuscin deposits [62]. GSEA implied that the low-risk group was enriched with immune pathways such as the B cell receptor (BCR) and T cell receptor (TCR) pathways, and had higher immune infiltration and immune score, which may be related to their better prognosis (Figs.…”

Section: Discussionmentioning

confidence: 99%

Identification and verification of aging-related lncRNAs for prognosis prediction and immune microenvironment in patients with head and neck squamous carcinoma

GAO¹,

SHI²,

Sun³

et al. 2023

Oncology Research

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Aging is highly associated with tumor formation and progression. However, little research has explored the association of aging-related lncRNAs (ARLs) with the prognosis and tumor immune microenvironment (TIME) of head and neck squamous cell carcinoma (HNSCC). RNA sequences and clinicopathological data of HNSCC patients and normal subjects were downloaded from The Cancer Genome Atlas. In the training group, we used Pearson correlation, univariate Cox regression, least absolute shrinkage/selection operator regression analyses, and multivariate Cox regression to build a prognostic model. In the test group, we evaluated the model. Multivariate Cox regression was done to screen out independent prognostic factors, with which we constructed a nomogram. Afterward, we demonstrated the predictive value of the risk scores based on the model and the nomogram using time-dependent receiver operating characteristics. Gene set enrichment analysis, immune correlation analysis, and half-maximal inhibitory concentration were also performed to reveal the different landscapes of TIME between risk groups and to predict immuno-and chemo-therapeutic responses. The most important LINC00861 in the model was examined in HNE1, CNE1, and CNE2 nasopharyngeal carcinoma cell lines and transfected into the cell lines CNE1 and CNE2 using the LINC00861-pcDNA3.1 construct plasmid. In addition, CCK-8, Edu, and SA-β-gal staining assays were conducted to test the biofunction of LINC00861 in the CNE1 and CNE2 cells. The signature based on nine ARLs has a good predictive value in survival time, immune infiltration, immune checkpoint expression, and sensitivity to multiple drugs. LINC00861 expression in CNE2 was significantly lower than in the HNE1 and CNE1 cells, and LINC00861 overexpression significantly inhibited the proliferation and increased the senescence of nasopharyngeal carcinoma cell lines. This work built and verified a new prognostic model for HNSCC based on ARLs and mapped the immune landscape in HNSCC. LINC00861 is a protective factor for the development of HNSCC.

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“…In particular, immunotherapy is influenced by the age of the tumor host [ 9 ] and it is evident that most cancers are diagnosed in patients over 60. In this context, Damien Maggiorani and Christian Beauséjour focus on immune response and immune checkpoint inhibitor (ICI) therapy in older patients [ 10 ]. This analysis is essentially based on the findings suggesting that immune cell fitness can be impaired in aging and senescence, leading to an inefficient response and clinical outcome [ 10 ].…”

Section: Autoimmunity and Antitumor Responsementioning

confidence: 99%

“…In this context, Damien Maggiorani and Christian Beauséjour focus on immune response and immune checkpoint inhibitor (ICI) therapy in older patients [ 10 ]. This analysis is essentially based on the findings suggesting that immune cell fitness can be impaired in aging and senescence, leading to an inefficient response and clinical outcome [ 10 ]. Furthermore, Kumar and colleagues contributed a new approach to improve the efficacy of ICI therapy by co-targeting molecular machineries involved in the modifications of specific RNA to overcome toxicities and drug resistance to antibodies to immune-checkpoint receptors.…”

Section: Autoimmunity and Antitumor Responsementioning

confidence: 99%

10th Anniversary of Cells: Advances in Cellular Immunology—Regulation of Autoimmune Response and Antitumor Reactivity: Are They Two Side of the Same Coin?

Poggi

2022

Cells

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Senescence and Aging: Does It Impact Cancer Immunotherapies?

Cited by 13 publications

References 167 publications

Therapy-induced senescence drives immunotherapy resistance by inducing an immunosuppressive tumor microenvironment

Therapy-induced senescence drives immunotherapy resistance by inducing an immunosuppressive tumor microenvironment

Identification and verification of aging-related lncRNAs for prognosis prediction and immune microenvironment in patients with head and neck squamous carcinoma

10th Anniversary of Cells: Advances in Cellular Immunology—Regulation of Autoimmune Response and Antitumor Reactivity: Are They Two Side of the Same Coin?

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