Targeting immune checkpoints: how to use natural killer cells for fighting against solid tumors

Ghaedrahmati, Farhoodeh; Esmaeil, Nafiseh; Abbaspour, Maryam

doi:10.1002/cac2.12394

Cited by 17 publications

(4 citation statements)

References 328 publications

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“…They are called the “first line of defense” because, different from T lymphocytes, they do not express antigen-specific T cell receptors but act against mutated cells without prior sensitization or clonal expansion [ 95 ]. NK cell adoptive immunotherapy failed to show efficacy in the treatment of solid tumors, partly due to the immunosuppressive TME and lack of NK cell specificity to the tumor [ 96 ].…”

Section: Aptamer-based Immune Strategies For Tnbc Treatmentmentioning

confidence: 99%

Aptamer-Based Strategies to Boost Immunotherapy in TNBC

Agnello

d’Argenio

Nilo

et al. 2023

Cancers

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The immune system (IS) may play a crucial role in preventing tumor development and progression, leading, over the last years, to the development of effective cancer immunotherapies. Nevertheless, immune evasion, the capability of tumors to circumvent destructive host immunity, remains one of the main obstacles to overcome for maximizing treatment success. In this context, promising strategies aimed at reshaping the tumor immune microenvironment and promoting antitumor immunity are rapidly emerging. Triple-negative breast cancer (TNBC), an aggressive breast cancer subtype with poor outcomes, is highly immunogenic, suggesting immunotherapy is a viable strategy. As evidence of this, already, two immunotherapies have recently become the standard of care for patients with PD-L1 expressing tumors, which, however, represent a low percentage of patients, making more active immunotherapeutic approaches necessary. Aptamers are short, highly structured, single-stranded oligonucleotides that bind to their protein targets at high affinity and specificity. They are used for therapeutic purposes in the same way as monoclonal antibodies; thus, various aptamer-based strategies are being actively explored to stimulate the IS’s response against cancer cells. The aim of this review is to discuss the potential of the recently reported aptamer-based approaches to boost the IS to fight TNBC.

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Section: Aptamer-based Immune Strategies For Tnbc Treatmentmentioning

confidence: 99%

Aptamer-Based Strategies to Boost Immunotherapy in TNBC

Agnello

d’Argenio

Nilo

et al. 2023

Cancers

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“…Researchers have stated that blocking immune checkpoints not only rescues NK cells from exhaustion but also increases their robust antitumor functions [36]. Deleting TIPE2 and CISH, two intracellular checkpoint genes, had a synergistic effect in preventing NK cell exhaustion as well as improving antitumor activity [36]. Previous research studies have shown that disrupting the PD-1 pathway induces the production of cytokines, which may in turn increase tumor infiltration [37].…”

Section: Overcoming the Viability Barriers Of Nk Cell-based Immunothe...mentioning

confidence: 99%

“…Lately, the status quo of reversing NK cell exhaustion has been targeting immune checkpoints. Researchers have stated that blocking immune checkpoints not only rescues NK cells from exhaustion but also increases their robust antitumor functions [36]. Deleting TIPE2 and CISH, two intracellular checkpoint genes, had a synergistic effect in preventing NK cell exhaustion as well as improving antitumor activity [36].…”

Section: Overcoming the Viability Barriers Of Nk Cell-based Immunothe...mentioning

confidence: 99%

Application of natural killer immunotherapy in blood cancers and solid tumors

Sayegh

2023

Current Opinion in Oncology

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Purpose of review Natural killer (NK) cells are innate lymphoid cells characterized by their ability to attack aberrant and cancerous cells. In contrast to the activation of T-cells, NK cell activation is controlled by the interaction of NK cell receptors and their target cells in a manner independent of antigen organization. Due to NK cells’ broad array of activation cues, they have gained great attention as a potential therapeutic agent in cancer immunotherapy. Recent findings Ex vivo activation, expansion, and genetic modifications, such as the addition of a chimeric antigen receptor (CAR), will allow the next generation of NK cells to enhance cytotoxicity, promote survival, and create “off-the-shelf” products. In addition to these that are poised to greatly enhance their clinical activity, the inherent lack of potential for causing graft-versus-host disease (GVHD) and cytokine release syndrome (CRS) suggest that CAR NK cells have the potential to be complementary to CAR-T cells as a component of therapeutic strategies for cancer. Summary In this review, we will provide a general understanding of NK cell biology, CAR-NK cell advantages over CAR-T cell therapy, barriers to making NK cell immunotherapy viable, and current NK cell clinical trials for hematological malignancies and solid tumors. The next generation of NK cells has potential to change the circumstances guiding present cancer immunotherapies.

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“…These checkpoints play a key role in balancing the activity of the immune system, enabling it to respond to pathogens and cancer cells while avoiding damage to healthy tissues. However, cancer cells can sometimes use these checkpoints to avoid being attacked by the immune system [35][36][37]. They express certain proteins that interact with checkpoint receptors on immune cells, effectively suppressing the immune response against cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Immune Checkpoint Pathway Expression in Lymphocyte Subpopulations in Patients with Common Variable Immunodeficiency and Chronic Lymphocytic Leukemia

Mertowska,

Mertowski,

Smolak

et al. 2023

Cancers

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This study aims to gain a deeper understanding of chronic lymphocytic leukemia (CLL) and common variable immunodeficiency (CVID) by studying immune cells and specific immune checkpoint signaling pathways. The analysis of the percentage of selected immune points and their ligands (PD-1/PD-L1, CTLA-4/CD86, and CD200R/CD200) on peripheral blood lymphocyte subpopulations was performed using flow cytometry, and additional analyses determining the serum concentration of the above-mentioned molecules were performed using enzyme immunoassay tests. The obtained results indicate several significant changes in the percentage of almost all tested molecules on selected subpopulations of T and B lymphocytes in both CVID and CLL patients in relation to healthy volunteers and between the disease subunits themselves. The results obtained were also supported by the analysis of the serum concentration of soluble molecules tested. By uncovering valuable insights, we hope to enhance our comprehension and management of these conditions, considering both immunodeficiencies and hematological malignancies. Understanding the role of these signaling pathways in disease development and progression may lead to the development of modern, personalized diagnostic and therapeutic strategies. Ultimately, this knowledge may enable the monitoring of the immune system in patients with CVID and CLL, paving the way for improved patient care in the future.

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Targeting immune checkpoints: how to use natural killer cells for fighting against solid tumors

Abstract: Natural killer (NK) cells are unique innate immune cells that mediate antiviral and anti-tumor responses. Thus, they might hold great potential for cancer immunotherapy. NK cell adoptive immunotherapy in humans has shown

Cited by 17 publications

References 328 publications

Aptamer-Based Strategies to Boost Immunotherapy in TNBC

Aptamer-Based Strategies to Boost Immunotherapy in TNBC

Application of natural killer immunotherapy in blood cancers and solid tumors

Immune Checkpoint Pathway Expression in Lymphocyte Subpopulations in Patients with Common Variable Immunodeficiency and Chronic Lymphocytic Leukemia

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