Therapeutic application of human type 2 innate lymphoid cells via induction of granzyme B-mediated tumor cell death

Li, Zhenlong; Ma, Rui; Tang, Hejun; Guo, Jiamin; Shah, Zahir; Zhang, Jianying; Liu, Ningyuan; Cao, Shuai; Marcucci, Guido; Artis, David; Caligiuri, Michael A.; Yu, Jianhua

doi:10.1016/j.cell.2023.12.015

Cited by 16 publications

(4 citation statements)

References 77 publications

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“…As shown in Figure 3a, immunofluorescence staining indicated that the expression of granzyme B in 4T1 cells cocultured with T lymphocytes was much higher than that in 4T1 cells without coculture of T lymphocytes. The clear bands (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) in Western blot analysis further verified the high expression of granzyme B in 4T1 cells after incubation with T lymphocytes (Figure 3b).…”

Section: Resultsmentioning

confidence: 58%

“…Granzyme B is the most important member of the granzyme family. ,− After it is released by CTLs, it can enter the target cells and activate the caspase cascade reaction, thus rapidly causing DNA breakage of target cells and leading to cell apoptosis. It can also directly migrate to the nucleus, cut a series of nuclear proteins, and start or promote nuclear apoptosis events. − Therefore, the detection of granzyme B can directly reflect the expression level of CTLs, and granzyme B can serve as an important immune-related biomarker to evaluate the therapeutic effect. − …”

Section: Introductionmentioning

confidence: 99%

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Development of Granzyme B-targeted Smart Positron Emission Tomography Probes for Monitoring Tumor Early Response to Immunotherapy

Fu,

Xi,

Cai

et al. 2024

ACS Nano

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Granzyme B is an immune-related biomarker that closely correlates with cytotoxic T lymphocytes (CTLs), and hence detecting the expression level of granzyme B can provide a dependable scheme for clinical immune response assessment. In this study, two positron emission tomography (PET) probes [ 18 F]SF-M-14 and [ 18 F]SF-H-14 targeting granzyme B are designed based on the intramolecular cyclization scaffold SF. [ 18 F]SF-M-14 and [ 18 F]SF-H-14 can respond to granzyme B and glutathione (GSH) to conduct intramolecular cyclization and selfassemble into nanoaggregates to enhance the retention of probe at the target site. Both probes are prepared with high radiochemical purity (>98%) and high stability in PBS and mouse serum. In 4T1 cells cocultured with T lymphocytes, [ 18 F]SF-M-14 and [ 18 F]SF-H-14 reach the maximum uptake of 6.71 ± 0.29 and 3.47 ± 0.09% ID/mg at 0.5 h, respectively, but they remain below 1.95 ± 0.22 and 1.47 ± 0.21% ID/mg in 4T1 cells without coculture of T lymphocytes. In vivo PET imaging shows that the tumor uptake in 4T1-tumor-bearing mice after immunotherapy is significantly higher (3.5 times) than that in the untreated group. The maximum tumor uptake of [ 18 F]SF-M-14 and [ 18 F]SF-H-14 in the mice treated with BEC was 4.08 ± 0.16 and 3.43 ± 0.12% ID/g, respectively, while that in the untreated mice was 1.04 ± 0.79 and 1.41 ± 0.11% ID/g, respectively. These results indicate that both probes have great potential in the early evaluation of clinical immunotherapy efficacy.

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Section: Resultsmentioning

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Development of Granzyme B-targeted Smart Positron Emission Tomography Probes for Monitoring Tumor Early Response to Immunotherapy

Fu,

Xi,

Cai

et al. 2024

ACS Nano

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“…Thereby, the inhibition of colorectal tumors was achieved through the direct killing of CD8 + T cells and the induction of apoptosis by granzyme B (Figure 9). 48 A related study induced melanoma regression by using a dipeptidyl peptidase 4 inhibitor to increase endogenous levels of CXCL10 indicating the important role of CXCL10 in tumor therapy. 49 Studies have also shown that increased CXCL10 expression at the tumor site is strongly associated with a favorable prognosis in various human cancers, revealing the link between CXCL10 and tumor prognosis.…”

Section: Discussionmentioning

confidence: 99%

Parabacteroides distasonis-Derived Outer Membrane Vesicles Enhance Antitumor Immunity Against Colon Tumors by Modulating CXCL10 and CD8+ T Cells

Liang,

Li,

Yang

et al. 2024

DDDT

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Given the potent immunostimulatory effects of bacterial outer membrane vesicles (OMVs) and the significant anti-colon tumor properties of Parabacteroides distasonis (Pd), this study aimed to elucidate the role and potential mechanisms of Pd-derived OMVs (Pd-OMVs) against colon cancer. Methods: This study isolated and purified Pd-OMVs from Pd cultures and assessed their characteristics. The effects of Pd-OMVs on CT26 cell uptake, proliferation, and invasion were investigated in vitro. In vivo, a CT26 colon tumor model was used to investigate the anti-colon tumor effects and underlying mechanisms of Pd-OMVs. Finally, we evaluated the biosafety of Pd-OMVs. Results: Purified Pd-OMVs had a uniform cup-shaped structure with an average size of 165.5 nm and a zeta potential of approximately −9.56 mV, and their proteins were associated with pathways related to immunity and apoptosis. In vitro experiments demonstrated that CT26 cells internalized the Pd-OMVs, resulting in a significant decrease in their proliferation and invasion abilities. Further in vivo studies confirmed the accumulation of Pd-OMVs in tumor tissues, which significantly inhibited the growth of colon tumors. Mechanistically, Pd-OMVs increased the expression of CXCL10, promoting infiltration of CD8 + T cells into tumor tissues and expression of pro-inflammatory factors TNF-α, IL-1β, and IL-6. Notably, Pd-OMVs demonstrated a high level of biosafety. Conclusion: This paper elucidates that Pd-OMVs can exert significant anti-colon tumor effects by upregulating the expression of the chemokine CXCL10, thereby increasing the infiltration of CD8 + T cells into tumors and enhancing antitumor immune responses. This suggests that Pd-OMVs may be developed as a novel nanoscale potent immunostimulant with great potential for application in tumor immunotherapy. As well as developed as a novel nano-delivery carrier for combination with other antitumor drugs.

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“… A fourth approach is the therapeutic transfer of ex vivo expanded ILC2s to induce tumor cell death. In a major breakthrough reported by Li et al [ 264 ], the researchers found that as a member of the cytolytic immune effector cell family, human ILC2s secrete granzymes that lyse tumor cells by inducing pyroptosis and/or apoptosis of tumor cells. Unlike CAR T-cell therapy, which requires specific characteristics, ILC2 can be isolated from healthy donors, which is a huge advantage.…”

Section: Potential Clinical and Therapeutic Applications Of Nk And Cd...mentioning

confidence: 99%

Natural Killer Cells and Cytotoxic T Cells: Complementary Partners against Microorganisms and Cancer

Vojdani,

Koksoy,

Vojdani

et al. 2024

Microorganisms

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Natural killer (NK) cells and cytotoxic T (CD8+) cells are two of the most important types of immune cells in our body, protecting it from deadly invaders. While the NK cell is part of the innate immune system, the CD8+ cell is one of the major components of adaptive immunity. Still, these two very different types of cells share the most important function of destroying pathogen-infected and tumorous cells by releasing cytotoxic granules that promote proteolytic cleavage of harmful cells, leading to apoptosis. In this review, we look not only at NK and CD8+ T cells but also pay particular attention to their different subpopulations, the immune defenders that include the CD56+CD16dim, CD56dimCD16+, CD57+, and CD57+CD16+ NK cells, the NKT, CD57+CD8+, and KIR+CD8+ T cells, and ILCs. We examine all these cells in relation to their role in the protection of the body against different microorganisms and cancer, with an emphasis on their mechanisms and their clinical importance. Overall, close collaboration between NK cells and CD8+ T cells may play an important role in immune function and disease pathogenesis. The knowledge of how these immune cells interact in defending the body against pathogens and cancers may help us find ways to optimize their defensive and healing capabilities with methods that can be clinically applied.

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Therapeutic application of human type 2 innate lymphoid cells via induction of granzyme B-mediated tumor cell death

Cited by 16 publications

References 77 publications

Development of Granzyme B-targeted Smart Positron Emission Tomography Probes for Monitoring Tumor Early Response to Immunotherapy

Development of Granzyme B-targeted Smart Positron Emission Tomography Probes for Monitoring Tumor Early Response to Immunotherapy

Parabacteroides distasonis-Derived Outer Membrane Vesicles Enhance Antitumor Immunity Against Colon Tumors by Modulating CXCL10 and CD8+ T Cells

Natural Killer Cells and Cytotoxic T Cells: Complementary Partners against Microorganisms and Cancer

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