miRNAs in NK Cell-Based Immune Responses and Cancer Immunotherapy

Pesce, Silvia; Greppi, Marco; Ferretti, Elisa; Obino, Valentina; Carlomagno, Simona; Rutigliani, Mariangela; Thorén, Fredrik B.; Sivori, Simona; Castagnola, Patrizio; Candiani, Simona; Marcenaro, Emanuela

doi:10.3389/fcell.2020.00119

Cited by 28 publications

(29 citation statements)

References 155 publications

(172 reference statements)

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“…In addition to mAbs targeting KIRs, alternative strategies to target the KIR/HLA-I axis are under investigation. As an example, a miRNA (miR146a-5p) targeting KIR2DL1/KIR2DL2 mRNA by abrogating their expression has been recently identified [60,61]. This result may be exploited to generate/increment the effect of NK-cell KIR-mismatching against HLA-I + tumor cells and thus improve the NK-mediated anti-tumor activity.…”

Section: Kirsmentioning

confidence: 99%

Cancer Immunotherapy by Blocking Immune Checkpoints on Innate Lymphocytes

Pesce¹,

Trabanelli

Vito

et al. 2020

Cancers

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Immune checkpoints refer to a plethora of inhibitory pathways of the immune system that play a crucial role in maintaining self-tolerance and in tuning the duration and amplitude of physiological immune responses to minimize collateral tissue damages. The breakdown of this delicate balance leads to pathological conditions, including cancer. Indeed, tumor cells can develop multiple mechanisms to escape from immune system defense, including the activation of immune checkpoint pathways. The development of monoclonal antibodies, targeting inhibitory immune checkpoints, has provided an immense breakthrough in cancer therapy. Immune checkpoint inhibitors (ICI), initially developed to reverse functional exhaustion in T cells, recently emerged as important actors in natural killer (NK)-cell-based immunotherapy. Moreover, the discovery that also helper innate lymphoid cells (ILCs) express inhibitory immune checkpoints, suggests that these molecules might be targeted on ILCs, to modulate their functions in the tumor microenvironment. Recently, other strategies to achieve immune checkpoint blockade have been developed, including miRNA exploiting systems. Herein, we provide an overview of the current knowledge on inhibitory immune checkpoints on NK cells and ILCs and we discuss how to target these innate lymphocytes by ICI in both solid tumors and hematological malignancies.

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Section: Kirsmentioning

confidence: 99%

Cancer Immunotherapy by Blocking Immune Checkpoints on Innate Lymphocytes

Pesce¹,

Trabanelli

Vito

et al. 2020

Cancers

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“…Non-coding RNAs play significant roles in the development, maturation, and effector functions of NK cells. They directly or indirectly control the cytotoxic ability and surface expression of immune checkpoints on NK cells, thus indicating their use in antitumor therapies ( 128 ). Zhu and co-workers concluded the regulatory effect of miR-20a, which is over-expressed in various cancers.…”

Section: Nk Cells and Other Dendritic Cellsmentioning

confidence: 99%

“…miR-150 and miR-203 increase tumor suppression; miR-155, miR-26a/b, miR-101, miR-363, etc. lead to decreased cell survival, cell cycle progression and miR-183 and miR-1245 are known to hamper NK killing activity in TME ( 128 ). Ou and colleagues elucidated the role of miR-153 and circ_0000977 in hypoxic TME.…”

Section: Nk Cells and Other Dendritic Cellsmentioning

confidence: 99%

Remodeling of Stromal Cells and Immune Landscape in Microenvironment During Tumor Progression

Arora

Pal

2021

Front. Oncol.

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The molecular understanding of carcinogenesis and tumor progression rests in intra and inter-tumoral heterogeneity. Solid tumors confined with vast diversity of genetic abnormalities, epigenetic modifications, and environmental cues that differ at each stage from tumor initiation, progression, and metastasis. Complexity within tumors studied by conventional molecular techniques fails to identify different subclasses in stromal and immune cells in individuals and that affects immunotherapies. Here we focus on diversity of stromal cell population and immune inhabitants, whose subtypes create the complexity of tumor microenvironment (TME), leading primary tumors towards advanced-stage cancers. Recent advances in single-cell sequencing (epitope profiling) approach circumscribes phenotypic markers, molecular pathways, and evolutionary trajectories of an individual cell. We discussed the current knowledge of stromal and immune cell subclasses at different stages of cancer development with the regulatory role of non-coding RNAs. Finally, we reported the current therapeutic options in immunotherapies, advances in therapies targeting heterogeneity, and possible outcomes.

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“…The expression of NK receptor ligands can also be regulated at post‐transcriptional level, through the action of several miRNAs 174,283,284 . In particular, tumor cells can overexpress miRNAs involved in the down‐regulation of NKG2D ligands.…”

Section: Tumor Escape Strategiesmentioning

confidence: 99%

“…281,282 The expression of NK receptor ligands can also be regulated at posttranscriptional level, through the action of several miRNAs. 174,283,284 In particular, tumor cells can overexpress miRNAs involved in the down-regulation of NKG2D ligands. For instance, MICA is targeted by different miRNAs, including miR-183 (up-regulated by TGF-), miR-20a, miR-146b-5p, and miR-25/93/106b.…”

Section: Modulation Of Cytotoxic Effector Moleculesmentioning

confidence: 99%

Escape of tumor cells from the NK cell cytotoxic activity

Cantoni

Wurzer

Thomas

et al. 2020

Journal of Leukocyte Biology

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In recent years, NK cells, initially identified as potent cytotoxic effector cells, have revealed an unexpected complexity, both at phenotypic and functional levels. The discovery of different NK cell subsets, characterized by distinct gene expression and phenotypes, was combined with the characterization of the diverse functions NK cells can exert, not only as circulating cells, but also as cells localized or recruited in lymphoid organs and in multiple tissues. Besides the elimination of tumor and virus-infected cells, these functions include the production of cytokines and chemokines, the regulation of innate and adaptive immune cells, the influence on tissue homeostasis. In addition, NK cells display a remarkable functional plasticity, being able to adapt to the environment and to develop a kind of memory. Nevertheless, the powerful cytotoxic activity of NK cells remains one of their most relevant properties, particularly in the antitumor response. In this review, the process of tumor cell recognition and killing mediated by NK cells, starting from the generation of cytolytic granules and recognition of target cell, to the establishment of the NK cell immunological synapse, the release of cytotoxic molecules, and consequent tumor cell death is described. Next, the review focuses on the heterogeneous mechanisms, either intrinsic to tumors or induced by the tumor microenvironment, by which cancer cells can escape the NK cell-mediated attack.

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miRNAs in NK Cell-Based Immune Responses and Cancer Immunotherapy

Cited by 28 publications

References 155 publications

Cancer Immunotherapy by Blocking Immune Checkpoints on Innate Lymphocytes

Cancer Immunotherapy by Blocking Immune Checkpoints on Innate Lymphocytes

Remodeling of Stromal Cells and Immune Landscape in Microenvironment During Tumor Progression

Escape of tumor cells from the NK cell cytotoxic activity

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