Natural killer cells and immune-checkpoint inhibitor therapy: Current knowledge and new challenges

Poggi, Alessandro; Zocchi, Maria Raffaella

doi:10.1016/j.omto.2021.11.016

Cited by 30 publications

(25 citation statements)

References 241 publications

(361 reference statements)

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“…This may also be one reason for the discrepancy in the effectiveness of immunotherapy in patients with different risk scores. ICI can prevent cancer cells from undergoing immune escape and has become an important treatment for malignancies [ 45 ]. In this study, 18 immune checkpoint genes were highly expressed in the high-risk group of patients.…”

Section: Discussionmentioning

confidence: 99%

The Value of m5C-Related lncRNAs in the Prognostic Assessment and Immunotherapy of Stomach Adenocarcinoma

Zhu

Kong

et al. 2022

BioMed Research International

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Long noncoding RNAs (lncRNAs) are closely associated with a variety of tumors, including stomach adenocarcinoma (STAD). However, the role of 5-methylcytosine- (m5C-) related lncRNAs in STAD is still uncertain. This study investigated the value of m5C-related lncRNAs in prognostic evaluation and immunotherapy of STAD. STAD transcriptome sequencing data were downloaded from The Cancer Genome Atlas (TCGA) database, and m5C-related lncRNAs were screened by Pearson correlation analysis. A prognostic m5C-related lncRNA signature (m5CRLSig) associated with STAD was established using univariate and multivariate Cox regression analysis. We constructed a prognostic risk model for STAD with six m5C-related lncRNAs. The receiver operating characteristic (ROC) curve was used to examine the predictive efficacy. Univariate and multifactorial Cox regression analysis and principal component analysis (PCA) validated m5CRLSig as an independent factor of STAD prognosis. The clinicopathological characteristics of the model showed higher risk scores for stages II-IV, grade 3, N1-3, and death status. The calibration curve of a nomogram revealed that the nomogram had an excellent predictive function for survival risk. Furthermore, the expression of six m5C-related lncRNAs in STAD and paracancerous tissues was detected by quantitative real-time PCR (qRT-PCR), which verified the feasibility of the m5CRLSig as a prognostic marker for STAD. m5C-related lncRNAs were linked to multiple immune-associated pathways, according to gene set enrichment analysis (GSEA). CIBERSORT analysis indicated that m5CRLSig was involved in immune cell infiltration. Risk score was associated with immune checkpoint gene expression, immune function scores, and chemotherapeutic drug sensitivity. Therefore, m5CRLSig can efficiently assess the prognosis of STAD patients and can be used as a biological marker for immunotherapy.

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Section: Discussionmentioning

confidence: 99%

The Value of m5C-Related lncRNAs in the Prognostic Assessment and Immunotherapy of Stomach Adenocarcinoma

Zhu

Kong

et al. 2022

BioMed Research International

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“…The combination of cellular therapy with immune checkpoint inhibition can mediate improved anti-tumor activity. For example, the ability of adoptive transfer of NK cells to augment checkpoint inhibition therapies has been investigated in hematologic and solid tumors models (143)(144)(145). iPSC-NK cells combined with PD-1 checkpoint blockade produced more inflammatory cytokines and exerted increased cytotoxicity.…”

Section: Nk Cells Enhance Anti-tumor Activity In Combination With Imm...mentioning

confidence: 99%

iPSC-Derived Natural Killer Cell Therapies - Expansion and Targeting

2022

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Treatment of cancer with allogeneic natural killer (NK) cell therapies has seen rapid development, especially use against hematologic malignancies. Clinical trials of NK cell-based adoptive transfer to treat relapsed or refractory malignancies have used peripheral blood, umbilical cord blood and pluripotent stem cell-derived NK cells, with each approach undergoing continued clinical development. Improving the potency of these therapies relies on genetic modifications to improve tumor targeting and to enhance expansion and persistence of the NK cells. Induced pluripotent stem cell (iPSC)-derived NK cells allow for routine targeted introduction of genetic modifications and expansion of the resulting NK cells derived from a clonal starting cell population. In this review, we discuss and summarize recent important advances in the development of new iPSC-derived NK cell therapies, with a focus on improved targeting of cancer. We then discuss improvements in methods to expand iPSC-derived NK cells and how persistence of iPSC-NK cells can be enhanced. Finally, we describe how these advances may combine in future NK cell-based therapy products for the treatment of both hematologic malignancies and solid tumors.

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“…By targeting the inhibitory ligands (programmed cell death ligand 1 - PD-L1) or inhibitory receptors (programmed cell death protein 1 - PD-1, cytotoxic T-lymphocyte-associated protein 4 - CTLA-4) with monoclonal antibodies, the immune response against tumors can be unleashed ( 144 ). It is clear that T cells are the main drivers of immune checkpoint inhibitor responses, but a role of NK cells herein has been proposed ( 145 ). Several reports find PD-1-dependent effects of NK cells in specific tumors including MM ( 146 ), Kaposi sarcoma ( 147 ), Hodgkin lymphoma ( 148 ) and head and neck cancer ( 149 ).…”

Section: Stat3 – a Potential Target To Enhance Immune Checkpoint Inhi...mentioning

confidence: 99%

The Multifaceted Role of STAT3 in NK-Cell Tumor Surveillance

et al. 2022

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Signal transducer and activator of transcription 3 (STAT3) is a member of the Janus kinase (JAK)-STAT pathway, which is one of the key pathways contributing to cancer. STAT3 regulates transcription downstream of many cytokines including interleukin (IL)-6 and IL-10. In cancer, STAT3 is mainly described as a tumor promoter driving tumor cell proliferation, resistance to apoptosis, angiogenesis and metastasis and aberrant activation of STAT3 is associated with poor prognosis. STAT3 is also an important driver of immune evasion. Among many other immunosuppressive mechanisms, STAT3 aids tumor cells to escape natural killer (NK) cell-mediated immune surveillance. NK cells are innate lymphocytes, which can directly kill malignant cells but also regulate adaptive immune responses and contribute to the composition of the tumor microenvironment. The inborn ability to lyse transformed cells renders NK cells an attractive tool for cancer immunotherapy. Here, we provide an overview of the role of STAT3 in the dynamic interplay between NK cells and tumor cells. On the one hand, we summarize the current knowledge on how tumor cell-intrinsic STAT3 drives the evasion from NK cells. On the other hand, we describe the multiple functions of STAT3 in regulating NK-cell cytotoxicity, cytokine production and their anti-tumor responses in vivo. In light of the ongoing research on STAT3 inhibitors, we also discuss how targeting STAT3 would affect the two arms of STAT3-dependent regulation of NK cell-mediated anti-tumor immunity. Understanding the complexity of this interplay in the tumor microenvironment is crucial for future implementation of NK cell-based immunotherapies.

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Natural killer cells and immune-checkpoint inhibitor therapy: Current knowledge and new challenges

Cited by 30 publications

References 241 publications

The Value of m5C-Related lncRNAs in the Prognostic Assessment and Immunotherapy of Stomach Adenocarcinoma

The Value of m5C-Related lncRNAs in the Prognostic Assessment and Immunotherapy of Stomach Adenocarcinoma

iPSC-Derived Natural Killer Cell Therapies - Expansion and Targeting

The Multifaceted Role of STAT3 in NK-Cell Tumor Surveillance

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