Prognostic significance of tumor infiltrating natural killer cells subset CD57 in patients with squamous cell lung cancer

Villegas, Francisco; Coca, Santiago; Villarrubia, V. G.; Jiménez, Rodrigo; Chillon, M.J.; Jareño, Javier; Zuil, Marcos; Callol, L.

doi:10.1016/s0169-5002(01)00292-6

Cited by 396 publications

(291 citation statements)

References 40 publications

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“…PD-L1 blockade also resulted in higher amounts of CD57 + NK cells, a subpopulation that have been reported to have a higher cytotoxic capacity with greater responsiveness via CD16 engagement and its presence correlated with better outcomes in squamous cell lung cancer. 40,41 …”

Section: Discussionmentioning

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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Section: Discussionmentioning

confidence: 99%

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

2018

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“…42 High levels of tumor infiltrating NK cells (TINKs) are associated with a favorable tumor outcome in patients with colorectal carcinoma, gastric carcinoma and squamous cell lung cancer, suggesting that NK-cell infiltration into tumor tissues represents a positive prognostic marker. [43][44][45] As described above, NK-cell recognition of tumor cells by inhibitory and activating receptors is complex, and the three recognition models-'missing-self', 'non-self' and 'stress-induced self'-might be used to sense missing-or altered-self cells. Activated NK cells are thus in a position to directly or indirectly exert their antitumor activity to control tumor growth and prevent the rapid dissemination of metastatic tumors by 'immunosurveillance' mechanisms ( Figure 1).…”

Section: Conception Of Nk Cellsmentioning

confidence: 99%

NK cell-based immunotherapy for malignant diseases

et al. 2013

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Natural killer (NK) cells play critical roles in host immunity against cancer. In response, cancers develop mechanisms to escape NK cell attack or induce defective NK cells. Current NK cell-based cancer immunotherapy aims to overcome NK cell paralysis using several approaches. One approach uses expanded allogeneic NK cells, which are not inhibited by self histocompatibility antigens like autologous NK cells, for adoptive cellular immunotherapy. Another adoptive transfer approach uses stable allogeneic NK cell lines, which is more practical for quality control and large-scale production. A third approach is genetic modification of fresh NK cells or NK cell lines to highly express cytokines, Fc receptors and/or chimeric tumor-antigen receptors. Therapeutic NK cells can be derived from various sources, including peripheral or cord blood cells, stem cells or even induced pluripotent stem cells (iPSCs), and a variety of stimulators can be used for large-scale production in laboratories or good manufacturing practice (GMP) facilities, including soluble growth factors, immobilized molecules or antibodies, and other cellular activators. A list of NK cell therapies to treat several types of cancer in clinical trials is reviewed here. Several different approaches to NK-based immunotherapy, such as tissue-specific NK cells, killer receptor-oriented NK cells and chemically treated NK cells, are discussed. A few new techniques or strategies to monitor NK cell therapy by non-invasive imaging, predetermine the efficiency of NK cell therapy by in vivo experiments and evaluate NK cell therapy approaches in clinical trials are also introduced.

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“…Individuals with a high NK cell activity have a reduced risk to develop cancer [121]. Moreover, increased numbers of NK cells in different types of tumors correlate with improved prognosis for cancer patients [2,106,107]. However, emerging evidence exists that NK cell function in the tumor microenvironment becomes impaired during tumor progression.…”

Section: Discussionmentioning

confidence: 99%

“…Functionally, CD57 + NK cells display reduced proliferative capacity, but are potent IFN-γ producers and show high lytic capacity when stimulated via CD16. Thus, high numbers of tumor-infiltrating CD57 + cells were correlated with improved prognosis of cancer patients with several malignancies including lung, gastric and colorectal cancer [2,106,107]. These early observations suggested that CD56 dim CD57 + NK cells might be effective during antitumor responses.…”

Section: Nk Cell Recruitment To the Tumor Sitementioning

confidence: 94%

Shaping of NK Cell Responses by the Tumor Microenvironment

Stojanović

Correia

Cerwenka

2012

Cancer Microenvironment

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Natural killer (NK) cells belong to the innate immune system and are potent cytolytic and cytokineproducing effector cells in response to tumor targets. NK cell based anti-tumor immunotherapy was so far mainly successful in patients with different types of leukemia. For instance, acute myeloid leukemia (AML) patients displayed a prolonged survival if transplanted with haploidentical stem cells giving rise to NK cells with a mismatch in inhibitory killer immunoglobulin receptors (KIRs) and recipients' HLA class I. Although promising results have been achieved with hematological tumors, solid tumors are in most cases poorly controlled by NK cells. Therapeutic protocols that aimed at improving NK cell responses in patients with solid malignancies succeeded in increasing NK cell numbers and functional responses of NK cells isolated from the patients' peripheral blood. However, in the majority of cases tumor progression and overall survival of patients were not significantly improved. There is increasing evidence that tumor-associated NK cells become gradually impaired during tumor progression compared to NK cells from peripheral blood and healthy tissues. Future protocols of NK cell based immunotherapy should integrate three important aspects to improve NK cell anti-tumor activity: facilitating NK cell migration to the tumor site, enhancing their infiltration into the tumor tissue and ensuring subsequent efficient activation in the tumor. This review summarizes the current knowledge of tumor-infiltrating NK cells and the influence of the tumor microenvironment on their phenotype and function.

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Prognostic significance of tumor infiltrating natural killer cells subset CD57 in patients with squamous cell lung cancer

Cited by 396 publications

References 40 publications

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

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

NK cell-based immunotherapy for malignant diseases

Shaping of NK Cell Responses by the Tumor Microenvironment

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