Prognostic value of peripheral blood natural killer cells in colorectal cancer

Tang, Yanping; Xie, Min; Li, Kezhi; Li, Jilin; Cai, Zhengmin; Hu, Bang-li

doi:10.1186/s12876-020-1177-8

Cited by 68 publications

(57 citation statements)

References 29 publications

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“…NLR and PLR were calculated. Details of the tumor location, degree of differentiation, and TNM staging (American Joint Committee on Cancer criteria, 8 th Edition) [ 10 ] were also collected. All the patients were followed up after treatment until December 2016 or death.…”

Section: Methodsmentioning

confidence: 99%

“…NK cells are good markers for the prognosis of cancers. Tang et al [ 10 ] showed that NK cells in the blood were an independent predictor of survival in CRC patients. A recent study reported that low NK cell counts in the circulation or tumor tissue before treatment were associated with poorer outcomes in patients with follicular lymphoma and diffuse large B cell lymphoma undergoing antibody-based therapy [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Percentage of Natural Killer (NK) Cells in Peripheral Blood Is Associated with Prognosis in Patients with Gastric Cancer: A Retrospective Study from a Single Center

Xie

Tang

et al. 2021

Med Sci Monit

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Background Natural killer (NK) cells are important for the prognosis of multiple cancers, but their prognostic value remains to be evaluated in patients with gastric cancer. Thus, this retrospective study was conducted at a single center to investigate the association between percentage of NK cells in the peripheral blood and prognosis in patients with gastric cancer. Material/Methods The data of 180 gastric cancer patients were collected. Univariate and multivariate Cox regression models were applied to screen candidate prognostic factors. A time-dependent receiver operating characteristic curve was employed to evaluate the ability of NK cells as a prognostic marker. Furthermore, we determined the correlation between the NK cells percentage and other parameters and their clinical significance. Results Patients with a higher percentage of NK cells survived longer than those with a lower percentage of NK cells. Cox analysis revealed that NK cells could be used as an independent indicator for patients with gastric cancer. The percentage of NK cells was positively correlated with lymphocyte count and albumin, but was negatively correlated with CA125 and neutrophil-lymphocyte ratio. The area under the curve for NK cells in predicting the 5-year survival rate for gastric cancer was 0.792. This increased to 0.830 upon combining NK cells with neutrophil-lymphocyte ratio. Patients at early T, N, and clinical stages possessed a significantly higher percentage of NK cells compared to those at advanced T, N, and clinical stages of gastric cancer. Conclusions Our results suggest that a higher percentage of NK cells predicts is associated with longer survival of gastric cancer patients and could serve as an independent prognostic biomarker.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Percentage of Natural Killer (NK) Cells in Peripheral Blood Is Associated with Prognosis in Patients with Gastric Cancer: A Retrospective Study from a Single Center

Xie

Tang

et al. 2021

Med Sci Monit

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“…Cytokines secreted by split-anergized NK cells play an important role in mediating tumor cell differentiation [ 38 , 40 , 41 ]. It was previously demonstrated that decreased NK cell counts, suppressed NK function, and the down-modulation of NK cell surface receptors in the peripheral blood and the tumor microenvironment were associated with poor prognoses in cancer patients [ 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ]. Our previous work also illustrated that NK cells of cancer patients and of tumor-bearing humanized-bone marrow/liver/thymus (BLT) mice mediated less cytotoxicity against cancer cells and secreted lower levels of cytokines [ 61 , 62 , 63 ].…”

Section: Introductionmentioning

confidence: 99%

ADCC against MICA/B Is Mediated against Differentiated Oral and Pancreatic and Not Stem-Like/Poorly Differentiated Tumors by the NK Cells; Loss in Cancer Patients due to Down-Modulation of CD16 Receptor

Kaur

Safaie

et al. 2021

Cancers

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Tumor cells are known to upregulate major histocompatibility complex-class I chain related proteins A and B (MICA/B) expression under stress conditions or due to radiation exposure. However, it is not clear whether there are specific stages of cellular maturation in which these ligands are upregulated or whether the natural killer (NK) cells differentially target these tumors in direct cytotoxicity or antibody-dependent cell cytotoxicity (ADCC). We used freshly isolated primary and osteoclast (OCs)-expanded NK cells to determine the degree of direct cytotoxicity or of ADCC using anti-MICA/B monoclonal antibodies (mAbs) against oral stem-like/poorly-differentiated oral squamous cancer stem cells (OSCSCs) and Mia PaCa-2 (MP2) pancreatic tumors as well as their well-differentiated counterparts: namely, oral squamous carcinoma cells (OSCCs) and pancreatic PL12 tumors. By using phenotypic and functional analysis, we demonstrated that OSCSCs and MP2 tumors were primary targets of direct cytotoxicity by freshly isolated NK cells and not by ADCC mediated by anti-MICA/B mAbs, which was likely due to the lower surface expression of MICA/B. However, the inverse was seen when their MICA/B-expressing differentiated counterparts, OSCCs and PL12 tumors, were used in direct cytotoxicity and ADCC, in which there was lower direct cytotoxicity but higher ADCC mediated by the NK cells. Differentiation of the OSCSCs and MP2 tumors by NK cell-supernatants abolished the direct killing of these tumors by the NK cells while enhancing NK cell-mediated ADCC due to the increased expression of MICA/B on the surface of these tumors. We further report that both direct killing and ADCC against MICA/B expressing tumors were significantly diminished by cancer patients’ NK cells. Surprisingly, OC-expanded NK cells, unlike primary interleukin-2 (IL-2) activated NK cells, were found to kill OSCCs and PL12 tumors, and under these conditions, we did not observe significant ADCC using anti-MICA/B mAbs, even though the tumors expressed a higher surface expression of MICA/B. In addition, differentiated tumor cells also expressed higher levels of surface epidermal growth factor receptor (EGFR) and programmed death-ligand 1(PDL1) and were more susceptible to NK cell-mediated ADCC in the presence of anti-EGFR and anti-PDL1 mAbs compared to their stem-like/poorly differentiated counterparts. Overall, these results suggested the possibility of CD16 receptors mediating both direct cytotoxicity and ADCC, resulting in the competitive use of these receptors in either direct killing or ADCC, depending on the differentiation status of tumor cells and the stage of maturation and activation of NK cells.

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“…NCRs mediate NK cell killing and IFNγ release [ 93 ]. The effects of NK levels on CRC outcomes is controversial with one study reporting above-median percentage of CD16+ NKT-like cells was associated with decreased disease-free survival for CRC patients [ 92 ], while another study found the percentage of NK cells in blood was an independent predictor of survival in CRC patients [ 94 ]. CD16 activates resting NK cells thru engagement with antibodies; however, NK cells may become exhausted and show lower cytotoxic activity thru CD16 stimulation [ 95 ].…”

Section: -Fu Modulates the Anti-tumor Immune Responsementioning

confidence: 99%

Fluoropyrimidine Modulation of the Anti-Tumor Immune Response―Prospects for Improved Colorectal Cancer Treatment

Gmeiner

2020

Cancers

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Chemotherapy modulates the anti-tumor immune response and outcomes depend on the balance of favorable and unfavorable effects of drugs on anti-tumor immunity. 5-Florouracil (5-FU) is widely used in adjuvant chemotherapy regimens to treat colorectal cancer (CRC) and provides a survival benefit. However, survival remains poor for CRC patients with advanced and metastatic disease and immune checkpoint blockade therapy benefits only a sub-set of CRC patients. Here we discuss the effects of 5-FU-based chemotherapy regimens to the anti-tumor immune response. We consider how different aspects of 5-FU’s multi-factorial mechanism differentially affect malignant and immune cell populations. We summarize recent studies with polymeric fluoropyrimidines (e.g., F10, CF10) that enhance DNA-directed effects and discuss how such approaches may be used to enhance the anti-tumor immune response and improve outcomes.

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Prognostic value of peripheral blood natural killer cells in colorectal cancer

Cited by 68 publications

References 29 publications

Percentage of Natural Killer (NK) Cells in Peripheral Blood Is Associated with Prognosis in Patients with Gastric Cancer: A Retrospective Study from a Single Center

Percentage of Natural Killer (NK) Cells in Peripheral Blood Is Associated with Prognosis in Patients with Gastric Cancer: A Retrospective Study from a Single Center

ADCC against MICA/B Is Mediated against Differentiated Oral and Pancreatic and Not Stem-Like/Poorly Differentiated Tumors by the NK Cells; Loss in Cancer Patients due to Down-Modulation of CD16 Receptor

Fluoropyrimidine Modulation of the Anti-Tumor Immune Response―Prospects for Improved Colorectal Cancer Treatment

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