Postoperative Natural Killer Cell Dysfunction: The Prime Suspect in the Case of Metastasis Following Curative Cancer Surgery

Market, Marisa; Tennakoon, Gayashan; Auer, Rebecca C.

doi:10.3390/ijms222111378

Cited by 19 publications

(14 citation statements)

References 301 publications

(431 reference statements)

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“…prostaglandin E2); anti‐inflammatory phase factors interleukin‐6 (IL‐6), interleukin‐10 (IL‐10) and transforming growth factor‐β1 (TGF‐β1); regulatory T‐cells; and myeloid‐derived suppressor cells (MDSCs). [2]…”

Section: Discussionmentioning

confidence: 99%

“…prostaglandin E2); anti-inflammatory phase factors interleukin-6 (IL-6), interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1); regulatory T-cells; and myeloidderived suppressor cells (MDSCs). [2] In summary, for NK-cell, B-cell and T-cell lymphocytes generally, exhaustion could be defined as an impaired state resulting from antigenic overstimulation, anergy could be defined as an impaired state resulting from inadequate stimulation of the activating receptors, senescence could be defined as an impaired state resulting from the ageing of the lymphocyte, and suppression could be defined as an impaired state resulting from the inhibiting actions of external non-antigenic factors.…”

Section: Lymphocyteexhaustionanergycellular Senescenceandsuppressionmentioning

confidence: 99%

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NK‐cell exhaustion, B‐cell exhaustion and T‐cell exhaustion—the differences and similarities

Roe¹

2022

Immunology

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T-cell exhaustion has been extensively researched, compared with B-cell exhaustion and NK-cell exhaustion, which have received considerably less attention; and there is less of a consensus on the precise definitions of NK-cell and B-cell exhaustion. NKcell exhaustion, B-cell exhaustion and T-cell exhaustion are examples of lymphocyte exhaustion, and they have several differences and similarities. Lymphocyte exhaustion is also frequently confused with anergy, cellular senescence and suppression, because these conditions can have significant overlapping similarities with exhaustion. An additional source of confusion is due to the fact that lymphocyte exhaustion is not a binary state, but instead has a spectrum of severity induced by different levels and duration of continuous antigenic stimulation. Concurrent multiple types of lymphocyte exhaustion are possible, and this situation is herein called poly-lymphocyte exhaustion. Poly-lymphocyte exhaustion for the same cancer or pathogen would be especially dangerous. As there are significant advantages for a pathogen by inducing poly-lymphocyte exhaustion in an immune system, there are pathogens with an evolved capability to induce poly-lymphocyte exhaustion. These pathogens may include certain manipulative viruses, bacteria, fungi and protozoan parasites.

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Section: Discussionmentioning

confidence: 99%

Section: Lymphocyteexhaustionanergycellular Senescenceandsuppressionmentioning

confidence: 99%

NK‐cell exhaustion, B‐cell exhaustion and T‐cell exhaustion—the differences and similarities

Roe¹

2022

Immunology

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“…High percentages of post-operative peripheral CD3(+), CD4(+), and CD8(+) T cells predict lower recurrence free survival in patients with CRC as they exert anti-tumor functions (65). The postoperative environment suppresses NK cells, which are critical mediators in the formation of metastases immediately following surgery (66). Moreover, it has been shown that absolute monocyte count decrease predicts worse overall survival and disease-free survival in esophageal squamous cell carcinoma undergoing curative resection (67).…”

Section: Discussionmentioning

confidence: 99%

Monitoring Pre- and Post-Operative Immune Alterations in Patients With Locoregional Colorectal Cancer Who Underwent Laparoscopy by Single-Cell Mass Cytometry

et al. 2022

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Surgical excision is currently the principal therapy for locoregional colorectal cancer (CRC). However, surgical trauma leads to controlled tissue damage, causing profound alterations in host immunity and, in turn, affecting post-operative outcomes. Surgery-induced immune alterations in CRC remain poorly defined. Here, single-cell mass cytometry was applied to serial blood samples collected pre-operatively, and on days 1, 3, and 7 post-operatively from 24 patients who underwent laparoscopic surgical resection of CRC to comprehensively monitor the perioperative phenotypic alterations in immune cells and dynamics of immune response. Characterization of immune cell subsets revealed that the post-operative immune response is broad but predominantly suppressive, supported by the decreases in total frequencies of circulating T cells and natural killer (NK) cells, as well as decreased HLA-DR expression on circulating monocytes. The proportion of T cells significantly decreased on day 1 and recovered to the pre-surgical level on day 3 after surgery. The frequency of monocytes was significantly elevated on day 1 after surgery and declined to baseline level on day 3. NK cells temporarily contracted on post-operative day 3. T cells, monocytes, DCs, NK cells, and B cells were partitioned into phenotypically different single-cell clusters. The dynamics of single-cell clusters were different from those of the bulk lineages. T cell clusters in the same response phase fluctuate inconsistently during the perioperative period. Comparing to the baseline levels, the frequencies of CD11b(+)CD33(+)CD14(+)CD16(−) classical monocytes expanded followed by contraction, whereas CD11b(+)CD33(+)CD14(high)CD16(low) intermediate monocytes remained unchanged; HLA-DR expression in monocytes were significantly reduced; the frequencies of intermediate CD56(bright)CD16(+) NK cell subsets increased; and the percentage of memory B lymphocytes were elevated after surgery. Post-operative pro- and anti-inflammatory cytokines were both altered. Furthermore, perioperative immune perturbations in some of the cell subsets were unrecovered within seven days after surgery. Chronological monitoring major immune lineages provided an overview of surgery-caused alterations, including cell augments and contractions and precisely timed changes in immune cell distribution in both innate and adaptive compartments, providing evidence for the interaction between tumor resection and immune modulation.

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“…These changes in the immune system may result in tumor proliferation, invasion and migration, and they are important factors leading to postoperative tumor recurrence and metastasis. 12–14 Currently, immunotherapy, including immunoadaptive infusion of T lymphocytes 15 and PD-1/PDL-1 inhibitors, 16 has achieved satisfactory results for cancer treatment. Immunosuppression in cancer patients constitutes the second clinical and biological feature of the tumor.…”

Section: Five Clinical and Biological Features Of Tumorsmentioning

confidence: 99%

Dezocine Has the Potential to Regulate the Clinical and Biological Features of Tumors

Hu¹,

Liu²,

Qiu³

et al. 2022

DDDT

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Cancer is the second leading cause of death following ischemic heart disease in the world and the primary clinical, social and economic burden. Surgical resection is the main measure for the treatment of the vast majority of solid tumors. However, the recurrence and metastasis of tumors occur at different periods after surgery in many cases undergoing radical tumor surgery, which is the main cause of death of tumor patients. Moreover, tumor patients are prone to suffer from mental depression, which may increase the morbidity and mortality of tumors. Tumors have a series of clinical biological signs with the following five main features: postoperative pain and cancerous pain; suppression of antitumor immunity; angiogenesis in tumors; proliferation, growth and metastasis of tumors; and mental depression. Surgery is the first treatment in the majority of cancer patients with solid tumors. Opioids are required for anesthesia and postoperative analgesia. For cancerous pain control, patients undergo surgery, and their quality of life of is improved. However, traditional opioids, such as morphine, may inhibit antitumor immunity, induce vascular growth of tumors and promote the proliferation, invasion and migration of cancer cells, and traditional opioids can induce a risk of somatic dependence. However, studies have found that not all opioids share the effects of immunosuppression, tumor proliferation promotion and angiogenesis induction. Dezocine, a novel opioid with specific pharmacological mechanisms, has been demonstrated to regulate the five clinical and biological features of tumors. We reviewed the preclinical and clinical studies of dezocine on postoperative pain and cancer pain in tumor patients as well as the immune system, tumor angiogenesis, tumor proliferation, tumor growth, tumor metastasis and mental depression. We proposed that dezocine may be the best choice of opioids for anesthesia and analgesia in cancer patients.

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Postoperative Natural Killer Cell Dysfunction: The Prime Suspect in the Case of Metastasis Following Curative Cancer Surgery

Cited by 19 publications

References 301 publications

NK‐cell exhaustion, B‐cell exhaustion and T‐cell exhaustion—the differences and similarities

NK‐cell exhaustion, B‐cell exhaustion and T‐cell exhaustion—the differences and similarities

Monitoring Pre- and Post-Operative Immune Alterations in Patients With Locoregional Colorectal Cancer Who Underwent Laparoscopy by Single-Cell Mass Cytometry

Dezocine Has the Potential to Regulate the Clinical and Biological Features of Tumors

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