Natural killer cells in cancer biology and therapy

Abstract

The tumor microenvironment is highly complex, and immune escape is currently considered an important hallmark of cancer, largely contributing to tumor progression and metastasis. Named for their capability of killing target cells autonomously, natural killer (NK) cells serve as the main effector cells toward cancer in innate immunity and are highly heterogeneous in the microenvironment. Most current treatment options harnessing the tumor microenvironment focus on T cell-immunity, either by promoting activating signals or suppressing inhibitory ones. The limited success achieved by T cell immunotherapy highlights the importance of developing new-generation immunotherapeutics, for example utilizing previously ignored NK cells. Although tumors also evolve to resist NK cell-induced cytotoxicity, cytokine supplement, blockade of suppressive molecules and genetic engineering of NK cells may overcome such resistance with great promise in both solid and hematological malignancies. In this review, we summarized the fundamental characteristics and recent advances of NK cells within tumor immunometabolic microenvironment, and discussed potential application and limitations of emerging NK cell-based therapeutic strategies in the era of presicion medicine.

Multiplexed Imaging Analysis of the Tumor-Immune Microenvironment Reveals Predictors of Outcome in Triple-Negative Breast Cancer

“…After Benjamini-Hochberg adjustment, there were no cell types with significant prognostic value. This includes the monocyte/neutrophil cell type 52 , the dendritic cell/monocyte cell type 53 , natural killer cells 54,55 , CD8+ T cells 24,56–60 , macrophages 61 , B cells 62 , CD4+ T cells 63,64 , and CD3+ T cells 65,66 .…”

Bioinformatics Analysis of Pivotal Module and Biomarkers Related to the Prognosis of Breast Cancer Based on Single-cell Transcriptome Data

“…Although the high total number of NK cells re ects a good survival rate, the in ltration and activation of NK cells vary greatly with different types of breast cancer. The heterogeneity of NK cells and their actual role in the microenvironment of breast cancer need to be further elucidated [20]. Tumor-associated macrophages (TAM) are the main component of breast cancer microenvironment [21].The increased density of macrophages in breast cancer tissues is related to the poor prognosis of patients.…”

Modulatory effects of gut microbiome in cancer immunotherapy: A novel paradigm for blockade of immune checkpoint inhibitors

“…NK cells are key players of the innate immune system, and are characterized by the surface expression of marker CD56 and the lack of CD3 expression. 41 This group of innate immune cells represents a heterogeneous subset of large granular lymphocytes, and constitutes nearly 5%-20% of all peripheral lymphocytes which are engaged in the clearance of virus-infected cells and lysis of tumor cells. [42][43][44] Beside their cytotoxic effector functions, NK cells are significantly involved in regulating the immune response by producing several cytokines and chemokines, mainly interferon-γ (IFNγ) and tumor necrosis factor (TNF)-α upon stimulation, to modulate other types of cells related to both the adaptive and innate immune responses.…”