scholarly journals Neutrophil and Natural Killer Cell Interactions in Cancers: Dangerous Liaisons Instructing Immunosuppression and Angiogenesis

Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1488
Author(s):  
Maria Teresa Palano ◽  
Matteo Gallazzi ◽  
Martina Cucchiara ◽  
Andrea De Lerma Barbaro ◽  
Daniela Gallo ◽  
...  
Keyword(s):  
Natural Killer ◽  
Immune Cells ◽  
Tumor Immunology ◽  
Molecular Mechanisms ◽  
Killer Cell ◽  
T Cell Subsets ◽  
Cell Contact ◽  
Effector Cells ◽  
Tumor Onset ◽  
Tumor Immune Microenvironment

The tumor immune microenvironment (TIME) has largely been reported to cooperate on tumor onset and progression, as a consequence of the phenotype/functional plasticity and adaptation capabilities of tumor-infiltrating and tumor-associated immune cells. Immune cells within the tumor micro (tissue-local) and macro (peripheral blood) environment closely interact by cell-to-cell contact and/or via soluble factors, also generating a tumor-permissive soil. These dangerous liaisons have been investigated for pillars of tumor immunology, such as tumor associated macrophages and T cell subsets. Here, we reviewed and discussed the contribution of selected innate immunity effector cells, namely neutrophils and natural killer cells, as “soloists” or by their “dangerous liaisons”, in favoring tumor progression by dissecting the cellular and molecular mechanisms involved.

scholarly journals Immunomodulatory effects of lenalidomide and pomalidomide on interaction of tumor and bone marrow accessory cells in multiple myeloma

Blood ◽  
2010 ◽  
Vol 116 (17) ◽  
pp. 3227-3237 ◽  
Author(s):  
Güllü Görgün ◽  
Elisabetta Calabrese ◽  
Ender Soydan ◽  
Teru Hideshima ◽  
Giulia Perrone ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Natural Killer ◽  
Immune Cells ◽  
Immune Cell ◽  
Interleukin 2 ◽  
Cytokine Signaling ◽  
Accessory Cell ◽  
Cell Contact ◽  
Effector Cells

Abstract The bone marrow (BM) microenvironment consists of extracellular-matrix and the cellular compartment including immune cells. Multiple myeloma (MM) cell and BM accessory cell interaction promotes MM survival via both cell-cell contact and cytokines. Immunomodulatory agents (IMiDs) target not only MM cells, but also MM cell-immune cell interactions and cytokine signaling. Here we examined the in vitro effects of IMiDs on cytokine signaling triggered by interaction of effector cells with MM cells and BM stroma cells. IMiDs diminished interleukin-2, interferonγ, and IL-6 regulator suppressor of cytokine signaling (SOCS)1 expression in immune (CD4T, CD8T, natural-killer T, natural-killer) cells from both BM and PB of MM patients. In addition, coculture of MM cells with healthy PBMCs induced SOCS1 expression in effector cells; conversely, treatment with IMiDs down-regulated the SOCS1 expression. SOCS1 negatively regulates IL-6 signaling and is silenced by hypermethylation in MM cells. To define the mechanism of inhibitory-cytokine signaling in effector cells and MM cells, we next analyzed the interaction of immune cells with MM cells that were epigenetically modified to re-express SOCS1; IMiDs induced more potent CTL responses against SOCS1 re-expressing–MM cells than unmodified MM cells. These data therefore demonstrate that modulation of SOCS1 may enhance immune response and efficacy of IMiDs in MM.

scholarly journals NKG2D Natural Killer Cell Receptor—A Short Description and Potential Clinical Applications

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1420
Author(s):  
Jagoda Siemaszko ◽  
Aleksandra Marzec-Przyszlak ◽  
Katarzyna Bogunia-Kubik
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Bacterial Infections ◽  
Killer Cell ◽  
Cell Receptor ◽  
Target Cells ◽  
Effector Cells ◽  
Stressed Cells ◽  
The Right ◽  
Nkg2d Receptor

Natural Killer (NK) cells are natural cytotoxic, effector cells of the innate immune system. They can recognize transformed or infected cells. NK cells are armed with a set of activating and inhibitory receptors which are able to bind to their ligands on target cells. The right balance between expression and activation of those receptors is fundamental for the proper functionality of NK cells. One of the best known activating receptors is NKG2D, a member of the CD94/NKG2 family. Due to a specific NKG2D binding with its eight different ligands, which are overexpressed in transformed, infected and stressed cells, NK cells are able to recognize and attack their targets. The NKG2D receptor has an enormous significance in various, autoimmune diseases, viral and bacterial infections as well as for transplantation outcomes and complications. This review focuses on the NKG2D receptor, the mechanism of its action, clinical relevance of its gene polymorphisms and a potential application in various clinical settings.

scholarly journals Functional and genomic profiling of effector CD8 T cell subsets with distinct memory fates

2008 ◽  
Vol 205 (3) ◽  
pp. 625-640 ◽  
Author(s):  
Surojit Sarkar ◽  
Vandana Kalia ◽  
W. Nicholas Haining ◽  
Bogumila T. Konieczny ◽  
Shruti Subramaniam ◽  
...  
Keyword(s):  
T Cells ◽  
Expression Profiles ◽  
Acute Infection ◽  
Killer Cell ◽  
Gene Expression Profiles ◽  
Antigenic Stimulation ◽  
T Cell Subsets ◽  
Genomic Profiling ◽  
Memory Cells ◽  
Effector Cells

An important question in memory development is understanding the differences between effector CD8 T cells that die versus effector cells that survive and give rise to memory cells. In this study, we provide a comprehensive phenotypic, functional, and genomic profiling of terminal effectors and memory precursors. Using killer cell lectin-like receptor G1 as a marker to distinguish these effector subsets, we found that despite their diverse cell fates, both subsets possessed remarkably similar gene expression profiles and functioned as equally potent killer cells. However, only the memory precursors were capable of making interleukin (IL) 2, thus defining a novel effector cell that was cytotoxic, expressed granzyme B, and produced inflammatory cytokines in addition to IL-2. This effector population then differentiated into long-lived protective memory T cells capable of self-renewal and rapid recall responses. Experiments to understand the signals that regulate the generation of terminal effectors versus memory precursors showed that cells that continued to receive antigenic stimulation during the later stages of infection were more likely to become terminal effectors. Importantly, curtailing antigenic stimulation toward the tail end of the acute infection enhanced the generation of memory cells. These studies support the decreasing potential model of memory differentiation and show that the duration of antigenic stimulation is a critical regulator of memory formation.

Comparing of pan-cancer tumor immune microenvironment.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15100-e15100
Author(s):  
Jiaan Ye ◽  
Longgang Cui ◽  
Xiaochen Zhao ◽  
Guanghui Lan
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Natural Killer Cell ◽  
Natural Killer ◽  
Cancer Patients ◽  
Killer Cell ◽  
Immune Microenvironment ◽  
Hepatobiliary Cancer ◽  
Tumor Immune Microenvironment ◽  
Pan Cancer

e15100 Background: Cancer treatment has entered the era of immune checkpoint inhibitors (ICI), but different tumors have different responses to ICI drugs. For example, non-small cell lung cancer and melanoma have higher response rates to ICIs than colorectal cancer and liver cancer patients. Previous studies have shown that tumor immune microenvironment have a great impact on the efficacy of ICI. Methods: This study retrospectively included pan-cancer patient specimens, using multiple fluorescent labeling immunohistochemistry to explore the differences in the immune microenvironment of different tumors. Shapiro-Wilk was used for normality test, and ANOVA or Kruskal Wallis test was used according to the results. Two-sided P < 0.05 was considered a significant difference. Results: The study included 308 patients, including 119 (38.6%) NSCLC patients, 72 (23.4%) Colorectal cancer patients, 51 (16.6%) Hepatobiliary cancer patients and 66 (21.4%) Others types of cancer patients. Among them, there was 192 (62.3%) Male, and 116 (37.7%) Female, and the median age was 57 (50-66). The proportion of CD8+ T cells and natural killer cell in tumor was statistically different. The proportion of CD8+ T cells in NSCLC, Colorectal cancer, Hepatobiliary cancer and others was 2.16%, 1%, 1.77% and 2.63%, p < 0.01; the proportion of natural killer cell was 16.44 %, 4.91%, 5.58% and 3.29%, p < 0.01. Conclusions: Different tumor types have different immune microenvironments. These results may provide valuable clues for future ICI trail design.

scholarly journals Prognostic significance of natural killer cell-associated markers in gastric cancer: quantitative analysis using multiplex immunohistochemistry

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hee Young Na ◽  
Yujun Park ◽  
Soo Kyung Nam ◽  
Jiwon Koh ◽  
Yoonjin Kwak ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
B Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Immune Cells ◽  
Nk Cell ◽  
Critical Role ◽  
Killer Cell ◽  
Prognostic Significance

Abstract Background Natural killer (NK) cells mediate the anti-tumoral immune response as an important component of innate immunity. The aim of this study was to investigate the prognostic significance and functional implication of NK cell-associated surface receptors in gastric cancer (GC) by using multiplex immunohistochemistry (mIHC). Methods We performed an mIHC on tissue microarray slides, including 55 GC tissue samples. A total of 11 antibodies including CD57, NKG2A, CD16, HLA-E, CD3, CD20, CD45, CD68, CK, SMA, and ki-67 were used. CD45 + CD3-CD57 + cells were considered as CD57 + NK cells. Results Among CD45 + immune cells, the proportion of CD57 + NK cell was the lowest (3.8%), whereas that of CD57 + and CD57- T cells (65.5%) was the highest, followed by macrophages (25.4%), and B cells (5.3%). CD57 + NK cells constituted 20% of CD45 + CD57 + immune cells while the remaining 80% were CD57 + T cells. The expression of HLA-E in tumor cells correlated with that in tumoral T cells, B cells, and macrophages, but not CD57 + NK cells. The higher density of tumoral CD57 + NK cells and tumoral CD57 + NKG2A + NK cells was associated with inferior survival. Conclusions Although the number of CD57 + NK cells was lower than that of other immune cells, CD57 + NK cells and CD57 + NKG2A + NK cells were significantly associated with poor outcomes, suggesting that NK cell subsets play a critical role in GC progression. NK cells and their inhibitory receptor, NKG2A, may be potential targets in GC.

scholarly journals P02.03 Automated cell type specific PD-L1 quantification by artificial intelligence using high throughput bleach & stain 15-marker multiplex fluorescence immunohistochemistry in human cancers

2021 ◽  
Vol 9 (Suppl 1) ◽  
pp. A8.2-A9
Author(s):  
NC Blessin ◽  
E Bady ◽  
T Mandelkow ◽  
C Yang ◽  
J Raedler ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Immune Cells ◽  
T Cell Subsets ◽  
Immune Microenvironment ◽  
L1 Data ◽  
Tumor Immune Microenvironment ◽  
Immune Phenotypes ◽  
Fluorescence Immunohistochemistry ◽  
Tumor Entities

BackgroundThe quantification of PD-L1 (programmed cell death ligand 1) has been used to predict patient’s survival, to characterize the tumor immune microenvironment, and to predict response to immune checkpoint therapies. However, a framework to assess the PD-L1 status with a high interobserver reproducibility on tumor cells and different types of immune cells has yet to be established.Materials and MethodsTo study the impact of PD-L1 expression on the tumor immune microenvironment and patient outcome, a framework for fully automated PD-L1 quantification on tumor cells and immune cells was established and validated. Automated PD-L1 quantification was facilitated by incorporating three different deep learning steps for the analysis of more than 80 different neoplasms from more than 10’000 tumor specimens using a bleach & stain 15-marker multiplex fluorescence immunohistochemistry panel (i.e., PD-L1, PD-1, CTLA-4, panCK, CD68, CD163, CD11c, iNOS, CD3, CD8, CD4, FOXP3, CD20, Ki67, CD31). Clinicopathological parameter were available for more than 30 tumor entities and overall survival data were available for 1517 breast cancer specimens.ResultsComparing the automated deep-learning based PD-L1 quantification with conventional brightfield PD-L1 data revealed a high concordance in tumor cells (p<0.0001) as well as immune cells (p<0.0001) and an accuracy of the automated PD-L1 quantification ranging from 90% to 95.2%. Across all tumor entities, the PD-L1 expression level was significantly higher in distinct macrophage/dendritic cell (DC) subsets (identified by CD68, CD163, CD11c, iNOS; p<000.1) and in macrophages/DCs located in the Stroma (p<0.0001) as compared to intratumoral macrophages/DC subsets. Across all different tumor entities, the PD-L1 expression was highly variable and distinct PD-L1 driven immune phenotypes were identified based on the PD-L1 intensity on both tumor and immune cells, the distance between non-exhausted T-cell subsets (i.e. PD-1 and CTLA-4 expression on CD3+CD8+ cytotoxic T-cells, CD3+CD4+ T-helper cells, CD3+CD4+FOXP3+ regulatory T-cells) and tumor cells as well as macrophage/(DC) subtypes. In breast cancer, the PD-L1 fluorescence intensity on tumor cells showed a significantly higher predictive performance for overall survival with an area under receiver operating curves (AUC) of 0.72 (p<0.0001) than the percentage of PD-L1+ tumor cells (AUC: 0.54). In PD-L1 positive as well as negative breast cancers a close spatial relationship between T- cell subsets (CD3+CD4±CD8±FOXP3±PD-1±CTLA-4±) and Macrophage/DC subsets (CD68±CD163±CD11c±iNOS) was found prognostic relevant (p<0.0001).ConclusionsIn conclusion, multiplex immunofluorescence PD-L1 assessment provides cutoff-free/continuous PD-L1 data which are superior to the conventional percentage of PD-L1+ tumor cells and of high prognostic relevance. The combined analysis of spatial PD-L1/PD-1 data and more than 20 different immune cell subtypes of the immune tumor microenvironment revealed distinct PD-L1 immune phenotypes.Disclosure InformationN.C. Blessin: None. E. Bady: None. T. Mandelkow: None. C. Yang: None. J. Raedler: None. R. Simon: None. C. Fraune: None. M. Lennartz: None. S. Minner: None. E. Burandt: None. D. Höflmayer: None. G. Sauter: None. S.A. Weidemann: None.

scholarly journals Malignant monoblasts can function as effector cells in natural killer cell and antibody-dependent cellular cytotoxicity assays

Blood ◽  
1981 ◽  
Vol 57 (5) ◽  
pp. 972-974 ◽  
Author(s):  
P Hokland ◽  
M Hokland ◽  
J Ellegaard
Keyword(s):  
Natural Killer ◽  
Killer Cell ◽  
Present Knowledge ◽  
In Vitro Cultures ◽  
Cellular Cytotoxicity ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
Effector Cells ◽  
Cytotoxicity Assays ◽  
Acute Monoblastic Leukemia

Abstract This is the first report describing natural killer (NK) and antibody- dependent cellular cytotoxicity (ADCC) of malignant monoblasts. Pure acute monoblastic leukemia was diagnosed in bone marrow aspirations from two patients by use of conventional cytochemical methods as well as multiple immunologic techniques including detection of ALL antigens and terminal transferase. The malignant cells were subsequently found to be potent effectors in NK and ADCC assays. Addition of partially purified alpha-interferon to the in vitro cultures was found to have an enhancing effect on NK activity, whereas no modulation was seen in ADCC. These findings are discussed in the light of our present knowledge of lymphoid NK cells.

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