Chemotherapy accelerates immune-senescence and functional impairments of Vδ2pos T cells in elderly patients affected by liver metastatic colorectal cancer

Bruni, Elena; Cazzetta, Valentina; Donadon, Matteo; Cimino, Matteo; Torzilli, Guido; Spata, Gianmarco; Leonardi, Gloria; Dieli, Francesco; Mikulak, Joanna; Mavilio, Domenico

doi:10.1186/s40425-019-0825-4

Cited by 40 publications

(41 citation statements)

References 24 publications

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“…In addition to optimizing the negative impacts of cryopreservation, an important consideration to optimize the health of the mixed γδ T-cell product is the timing with which the cells will be administered to patients during a regimen of chemotherapy. Chemotherapy negatively impacts the cytotoxicity of resident γδ T cells (56), suggesting that it could also negatively impact cells being infused into a patient if the two treatments are administered closely together. Further studies will be necessary to determine the impacts of chemotherapy on the mixed γδ T cell product and to optimize the course of treatment.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Donor Variability for γδ T Cell ex vivo Expansion and Development of an Allogeneic γδ T Cell Immunotherapy

et al. 2020

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Section: Discussionmentioning

confidence: 99%

Characterization of Donor Variability for γδ T Cell ex vivo Expansion and Development of an Allogeneic γδ T Cell Immunotherapy

et al. 2020

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“…192 However, chemotherapy accelerated immune-senescence and functional impairment of the tumorinfiltrating Vδ2 + T cell subset from liver metastases in patients with CRC, observed as a relative increase in terminally differentiated CD27 neg /CD45RA pos (TEMRA) cells and increased expression of the senescence marker CD57, coupled with impairments in cytotoxicity and production of TNF-α and IFN-γ. 193 Additionally, significantly lower expression of IL-2 and IL-21 in γδ T cells was observed in HCC patients compared with healthy control volunteers, accounting for their reduced cytotoxic capacity. 194 Degranulation and IFN-γ secretion were also substantially impaired in HCC-infiltrating γδ T cells, partially mediated directly by Tregs in a TGF-β-and IL-10dependent manner.…”

Section: Viral Infectionmentioning

confidence: 99%

Innate lymphocytes: pathogenesis and therapeutic targets of liver diseases and cancer

Chen

Tian

2020

Cell Mol Immunol

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The liver is a lymphoid organ with unique immunological properties, particularly, its predominant innate immune system. The balance between immune tolerance and immune activity is critical to liver physiological functions and is responsible for the sensitivity of this organ to numerous diseases, including hepatotropic virus infection, alcoholic liver disease, nonalcoholic fatty liver disease, autoimmune liver disease, and liver cancer, which are major health problems globally. In the past decade, with the discovery of liver-resident natural killer cells, the importance of innate lymphocytes with tissue residency has gradually become the focus of research. In this review, we address the current knowledge regarding hepatic innate lymphocytes with unique characteristics, including NK cells, ILC1/2/3s, NKT cells, γδ T cells, and MAIT cells, and their potential roles in liver homeostasis maintenance and the progression of liver diseases and cancer. A better understanding of the immunopathogenesis of hepatic innate lymphocytes will be helpful for proposing effective treatments for liver diseases and cancer.

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“…However, while the frequencies of CD57+ Vδ2+ do not generally increase with aging, a recent study by Bruni et al 2019 shows that elderly (>60 years old) liver metastatic colorectal cancer patients reveal significantly higher frequencies of CD57+ Vδ2+, in both the periphery and the liver, after undergoing chemotherapy, as compared to younger patients [128]. This could imply that the Vδ2+ in the elderly could still be vulnerable to external stressors such as chemotherapy, infections and radiotherapy.…”

Section: Homeostasis Of γδ T Cells In Tissuesmentioning

confidence: 96%

The Aging of γδ T Cells

Lau

Fülöp

et al. 2020

Cells

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In the coming decades, many developed countries in the world are expecting the "greying" of their populations. This phenomenon poses unprecedented challenges to healthcare systems. Aging is one of the most important risk factors for infections and a myriad of diseases such as cancer, cardiovascular and neurodegenerative diseases. A common denominator that is implicated in these diseases is the immune system. The immune system consists of the innate and adaptive arms that complement each other to provide the host with a holistic defense system. While the diverse interactions between multiple arms of the immune system are necessary for its function, this complexity is amplified in the aging immune system as each immune cell type is affected differently-resulting in a conundrum that is especially difficult to target. Furthermore, certain cell types, such as γδ T cells, do not fit categorically into the arms of innate or adaptive immunity. In this review, we will first introduce the human γδ T cell family and its ligands before discussing parallels in mice. By covering the ontogeny and homeostasis of γδ T cells during their lifespan, we will better capture their evolution and responses to age-related stressors. Finally, we will identify knowledge gaps within these topics that can advance our understanding of the relationship between γδ T cells and aging, as well as age-related diseases such as cancer.Their well-characterized roles further imply the physiological importance of age-associated T-cell adaptations, which garners the widespread scientific interest that has contributed to the current depth of T-cell-related investigations [14,15].T cells can essentially be classified into the adaptive arm, although minority subsets exhibit an innate phenotype. Adaptive T cells include those expressing an αβ T cell receptor (TCR) at their surface and "innate-like" T cells are comprised of T cells expressing a γδ TCR, mucosal associated invariant T (MAIT), invariant natural killer T (iNKT) and germline-encoded mycolyl lipid-reactive (GEMT) [16]. This classification is based on their response speed when encountering new antigens and the ability to form memory cells that persist in long-term immunosurveillance. In this review, we will focus on γδ T cells and their contextual importance in cancer immunosurveillance, and on the reactivation of latent infections such as tuberculosis and virus-infected cells, as these topics require consolidation in the literature but are often neglected in the aging context.First, we will describe γδ T cells and their respective ligands in both mice and human. Next, we will analyze γδ T cells from cradle to grave (i.e., development to old age) to understand their aging trajectory during lifespan. Finally, we will suggest future developments that are necessary for our comprehension of how γδ T cells subsets are affected during the aging process. A better understanding of γδ T cell biology should enable scientists to tailor optimized immunotherapy that targets age-associated immune impairments in th...

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Chemotherapy accelerates immune-senescence and functional impairments of Vδ2pos T cells in elderly patients affected by liver metastatic colorectal cancer

Cited by 40 publications

References 24 publications

Characterization of Donor Variability for γδ T Cell ex vivo Expansion and Development of an Allogeneic γδ T Cell Immunotherapy

Characterization of Donor Variability for γδ T Cell ex vivo Expansion and Development of an Allogeneic γδ T Cell Immunotherapy

Innate lymphocytes: pathogenesis and therapeutic targets of liver diseases and cancer

The Aging of γδ T Cells

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