NK cells and cancer: you can teach innate cells new tricks

Morvan, Maelig; Lanier, Lewis L.

doi:10.1038/nrc.2015.5

Cited by 900 publications

(853 citation statements)

References 188 publications

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“…Increasing evidence supports their role in influencing the key components of adaptive immunity. This is mediated largely by their potent and early secretion of IFN-γ, which helps shape the immune tumor microenvironment by activating the effectors of adaptive immunity, particularly Th1 and myeloid cells (31,32). This ability to influence adaptive immunity as well as their innate tumor cytolytic capability implicates NK cells as key effectors of antitumor immunity.…”

Section: Resultsmentioning

confidence: 99%

“…This ability to influence adaptive immunity as well as their innate tumor cytolytic capability implicates NK cells as key effectors of antitumor immunity. As a result, the blockade of immunoregulatory NK cell checkpoint receptors has garnered significant interest (32)(33)(34). Agents (e.g., lirilumab) targeting NK cell inhibitory receptors, such as killer cell immunoglobulin-like receptor (KIR), are the subject of intense preclinical/clinical investigation as a monotherapy or in combination with other checkpoint inhibitors.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

The head and neck cancer immune landscape and its immunotherapeutic implications

Mandal¹,

Şenbabaoğlu

Desrichard³

et al. 2016

JCI Insight

591

613

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

The head and neck cancer immune landscape and its immunotherapeutic implications

Mandal¹,

Şenbabaoğlu

Desrichard³

et al. 2016

JCI Insight

591

613

View full text Add to dashboard Cite

“…This could be extended in the future to help, for example, sperm donors with the lowest risk of adverse pregnancy outcomes in assisted reproduction. In‐depth understanding of the molecular pathways that control NK cells will be critical to the therapeutic manipulation and in adoptive transfer strategies of these powerful lymphocytes,234 such as in cancer immunotherapy 16, 29, 235, 236. Immune‐modulation therapies that alter NK and T‐cell function are already in development.…”

Section: Therapeutic Interventionmentioning

confidence: 99%

Deciphering the killer‐cell immunoglobulin‐like receptor system at super‐resolution for natural killer and T‐cell biology

et al. 2016

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SummaryKiller‐cell immunoglobulin‐like receptors (KIRs) are components of two fundamental biological systems essential for human health and survival. First, they contribute to host immune responses, both innate and adaptive, through their expression by natural killer cells and T cells. Second, KIR play a key role in regulating placentation, and hence reproductive success. Analogous to the diversity of their human leucocyte antigen class I ligands, KIR are extremely polymorphic. In this review, we describe recent developments, fuelled by methodological advances, that are helping to decipher the KIR system in terms of haplotypes, polymorphisms, expression patterns and their ligand interactions. These developments are delivering deeper insight into the relevance of KIR in immune system function, evolution and disease.

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“…NK cells not only produce IFNγ and other cytokines, which are secreted upon recognition of the tumor, but also recruit and orchestrate responses by other immune cells such as T- and dendritic cells in the tumor bed. 7,8 (reviewed in 9,10 ) Furthermore, their direct killing of tumor cells leads to release of tumor antigens along with cytokines which likely primes the adaptive immune response for better tumor control. 11,12 …”

Section: Introductionmentioning

confidence: 99%

PD-L1 blockade enhances anti-tumor efficacy of NK cells

2018

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Anti-PD-1/anti-PD-L1 therapies have shown success in cancer treatment but responses are limited to ~ 15% of patients with lymphocyte infiltrated, PD-L1 positive tumors. Hence, strategies that increase PD-L1 expression and tumor infiltration should make more patients eligible for PD-1/PD-L1 blockade therapy, thus improving overall outcomes. PD-L1 expression on tumors is induced by IFNγ, a cytokine secreted by NK cells. Therefore, we tested if PM21-particle expanded NK cells (PM21-NK cells) induced expression of PD-L1 on tumors and if anti-PD-L1 treatment enhanced NK cell anti-tumor efficacy in an ovarian cancer model. Studies here showed that PM21-NK cells secrete high amounts of IFNγ and that adoptively transferred PM21-NK cells induce PD-L1 expression on SKOV-3 cells in vivo. The induction of PD-L1 expression on SKOV-3 cells coincided with the presence of regulatory T cells (Tregs) in the abdominal cavity and within tumors. In in vitro experiments, anti-PD-L1 treatment had no direct effect on cytotoxicity or cytokine secretion by predominantly PD-1 negative PM21-NK cells in response to PD-L1+ targets. However, significant improvement of NK cell anti-tumor efficacy was observed in vivo when combined with anti-PD-L1. PD-L1 blockade also resulted in increased in vivo NK cell persistence and retention of their cytotoxic phenotype. These results support the use of anti-PD-L1 in combination with NK cell therapy regardless of initial tumor PD-L1 status and indicate that NK cell therapy would likely augment the applicability of anti-PD-L1 treatment.

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NK cells and cancer: you can teach innate cells new tricks

Cited by 900 publications

References 188 publications

The head and neck cancer immune landscape and its immunotherapeutic implications

The head and neck cancer immune landscape and its immunotherapeutic implications

Deciphering the killer‐cell immunoglobulin‐like receptor system at super‐resolution for natural killer and T‐cell biology

PD-L1 blockade enhances anti-tumor efficacy of NK cells

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