T cell immune awakening in response to immunotherapy is age-dependent

Salih, Zena; Banyard, Antonia; Tweedy, Joshua; Galvani, Elena; Middlehurst, Philippa; Mills, Sarah; Weightman, John; Gupta, Avinash; Lorigan, Paul; Zhou, Cong; Dhomen, Nathalie; Valpione, Sara; Marais, Richard

doi:10.1016/j.ejca.2021.11.015

Cited by 5 publications

(4 citation statements)

References 23 publications

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“…Knowledge about multiple clinical variables is essential for precision immune-oncology and clinical decision making. By examining the clinical characteristics of patients with melanoma treated with first-line anti-PD-1 mAb, Zena et al observed age-related effects on TCR repertoire evolution and T IE cell expansion, showing that age influences T-cell reinvigoration by ICI therapy and, therefore, that it should be included among the biomarkers used to monitor responses to immunotherapy [ 105 ]. Additional research suggested that T-cell clones shared between blood and tumor (overlapping clones) are those more informative on the clinical outcome, as a higher frequency of overlapping clones within peripheral CD8 + T cells before anti-PD-1 treatment was associated with a favorable clinical response [ 106 – 108 ].…”

Section: Introductionmentioning

confidence: 99%

T-cell repertoire diversity: friend or foe for protective antitumor response?

Porciello¹,

Franzese

D’Ambrosio³

et al. 2022

J Exp Clin Cancer Res

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Profiling the T-Cell Receptor (TCR) repertoire is establishing as a potent approach to investigate autologous and treatment-induced antitumor immune response. Technical and computational breakthroughs, including high throughput next-generation sequencing (NGS) approaches and spatial transcriptomics, are providing unprecedented insight into the mechanisms underlying antitumor immunity. A precise spatiotemporal variation of T-cell repertoire, which dynamically mirrors the functional state of the evolving host-cancer interaction, allows the tracking of the T-cell populations at play, and may identify the key cells responsible for tumor eradication, the evaluation of minimal residual disease and the identification of biomarkers of response to immunotherapy. In this review we will discuss the relationship between global metrics characterizing the TCR repertoire such as T-cell clonality and diversity and the resultant functional responses. In particular, we will explore how specific TCR repertoires in cancer patients can be predictive of prognosis or response to therapy and in particular how a given TCR re-arrangement, following immunotherapy, can predict a specific clinical outcome. Finally, we will examine current improvements in terms of T-cell sequencing, discussing advantages and challenges of current methodologies.

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Section: Introductionmentioning

confidence: 99%

T-cell repertoire diversity: friend or foe for protective antitumor response?

Porciello¹,

Franzese

D’Ambrosio³

et al. 2022

J Exp Clin Cancer Res

View full text Add to dashboard Cite

show abstract

“…Additionally, the epidemiologic characteristics and clinical treatments of GBM exacerbated systemic immunosuppression. First, the median age diagnosis of GBM is 64 years, and patients are mainly composed of elderly patients with age-related immunosuppression, whose immunity are significantly weaker than that of younger patients, and whose bone marrow and thymus produce significant fewer T cells [23][24][25][26] ; Second, standard-of-care can cause iatrogenic immunosuppression and lead to systemic lymphopenia, termed treatmentrelated lymphopenia 7,27,28 ; Third, dexamethasone, the most often used to alleviate brain edema in GBM patients, also induces systemic depletion of naïve and memory T cells but increases immunosuppressive myeloid cells 29 . The prevailing immune-modulating therapies mainly focus on remodeling TME, aiming to overcome local immunosuppression to promote effector T cells infiltration and reinforce immune response against tumor 30 .…”

mentioning

confidence: 99%

Reprogramming systemic and local immune function to empower immunotherapy against glioblastoma

et al. 2023

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The limited benefits of immunotherapy against glioblastoma (GBM) is closely related to the paucity of T cells in brain tumor bed. Both systemic and local immunosuppression contribute to the deficiency of tumor-infiltrating T cells. However, the current studies focus heavily on the local immunosuppressive tumor microenvironment but not on the co-existence of systemic immunosuppression. Here, we develop a nanostructure named Nano-reshaper to co-encapsulate lymphopenia alleviating agent cannabidiol and lymphocyte recruiting cytokine LIGHT. The results show that Nano-reshaper increases the number of systemic T cells and improves local T-cell recruitment condition, thus greatly increasing T-cell infiltration. When combined with immune checkpoint inhibitor, this therapeutic modality achieves 83.3% long-term survivors without recurrence in GBM models in male mice. Collectively, this work unveils that simultaneous reprogramming of systemic and local immune function is critical for T-cell based immunotherapy and provides a clinically translatable option for combating brain tumors.

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“…So, downregulating these kinds of checkpoints could activate T cells to have stronger anti-cancer capacities. [ 16 ] PD-1 had recently been an important and hopeful checkpoint. PD-1 inhibitor-nivolumab played a significant role in anticarcinogenic actions, which had been proved by several phase II to III clinical trials.…”

Section: Discussionmentioning

confidence: 99%

The risks of hematological toxicities of nivolumab in cancer patients: A PRISMA-compliant meta-analysis

et al. 2022

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Background: Nivolumab is the human programmed cell death-1 (PD-1)-blocking antibody showing significant effect in many refractory cancers. However, little is known about its risks of hematological toxicities, rare but clinically serious and potentially life-threatening adverse events. We want to explore whether nivolumab can increase the risks of hematological toxicities compared with other immunotherapy or chemotherapy drugs. Method: The databases of PubMed, Embase, Web of science, and CNKI were searched. We used the medical subject heading terms “Nivolumab” plus keyword “Nivolumab” to search studies published from August 1990 to October 2021. For the included articles, we calculated the relative risks and the corresponding 95% confidence intervals (CIs) for the risks of anemia, neutropenia, and leukopenia in patients treated with nivolumab versus control drugs. Results: Five original articles on the nivolumab trials were identified with 2399 patients enrolled in this meta-analysis. The relative risks of anemia, neutropenia, and leukopenia were 0.343 (95% CI: 0.177–0.663; P = .001), 0.020 (95% CI: 0.008–0.053; P = .000), and 0.054 (95% CI: 0.015–0.191; P = .000), respectively. Conclusion: The PD-1 inhibitor-nivolumab did not increase the risk of anemia, neutropenia and leukopenia. It may enhance awareness about lower risks of hematological toxicities when choosing nivolumab as PD-1 inhibitor among clinicians.

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T cell immune awakening in response to immunotherapy is age-dependent

Cited by 5 publications

References 23 publications

T-cell repertoire diversity: friend or foe for protective antitumor response?

T-cell repertoire diversity: friend or foe for protective antitumor response?

Reprogramming systemic and local immune function to empower immunotherapy against glioblastoma

The risks of hematological toxicities of nivolumab in cancer patients: A PRISMA-compliant meta-analysis

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