Clinical implications of natural killer (NK) cytotoxicity in patients with squamous cell carcinoma of the uterine cervix

Vaquer, S.; Zurdo, Julia; Osa, E.López de la; Heros, J.Alvarez de los; López-García, N.; Álvarez-Mon, Melchor

doi:10.1016/0090-8258(90)90114-z

Cited by 19 publications

(15 citation statements)

References 9 publications

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“…Martimbeau et al [22] observed a 53% 5-year survival in patients with pelvic node metastases, and 92% when there were no métastasés; similarly a sig nificantly higher percentage of patients with pelvic node métastasés recurred than did patients without métastasés (33 vs. 7.3%) [23], Previously, other authors [16][17][18][19] analyzed natural im mune reactivity in patients with invasive carcinoma, starting from clinical and experimental observations which had pointed out the existence of immunologic host response against tumor cells. In particular, our results are in agreement with those of Balaram et al [ 18] and Vaquer et al [19] who proved a close relationship between the diminution of natural killer activity and metastatic spread of the cervical disease, suggesting that immunolog ical derangement is an important factor in the regulation of neoplastic growth, probably related to the prognostic evolution of the disease. However, the limit of these stud ies was the absence of a prospective evaluation of natural immune reactivity; only a longitudinal study during fol low-up of patients with cervical carcinoma, which analy ses immune reactivity before and after disease progres sion, may ascertain the cellular mechanisms implicated in this association and their meaning.…”

Section: Discussionmentioning

confidence: 99%

Natural Killer Cell Activity in Patients with Invasive Cervical Carcinoma: Importance of a Longitudinal Evaluation in Follow-Up

Garzetti¹,

Ciavattini²,

Muzzioli

et al. 1995

Gynecol Obstet Invest

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Objective: To analyze longitudinally the basal natural killer cell activity in patients with invasive cervical carcinoma, the natural cytotoxicity was related to the most important known prognostic factors, and evaluated with respect to the clinical outcome of cervical disease. Materials and Methods: Forty-six patients with histologically proven invasive cervical carcinoma treated and followed at the Institute of Gynecology and Obstetrics, Ancona University, Salesi Hospital, were consecutively recruited from 1989 to 1992 and included into the study. For immunologic investigation, natural killer cell activity and peripheral blood T-lymphocyte subsets were tested before primary treatment and during the follow-up period, every 6 months. Natural killer activity was determined by target cell retention of the fluorescent dye carboxyfluorescein diacetate; the K 562 cell line was used as target cells. Results: A significant inverse relationship was observed between natural killer activity and disease stage (p = 0.001); patients with stage IV disease had the lowest level of natural cytotoxicity. The reduction of natural cytotoxicity was not accompanied by any alteration of lymphocyte distribution. The longitudinal analysis showed an increase of natural killer activity after surgical removal of the tumor, persisting during the follow-up, but all the 9 patients who recurred showed, at the time of disease recurrence, a significant decrease of their natural cytotoxic potential. Conclusion: Natural killer cell activity seems to be a functional index of immune status, significantly related to the stage and the clinical outcome of disease.

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Section: Discussionmentioning

confidence: 99%

Natural Killer Cell Activity in Patients with Invasive Cervical Carcinoma: Importance of a Longitudinal Evaluation in Follow-Up

Garzetti¹,

Ciavattini²,

Muzzioli

et al. 1995

Gynecol Obstet Invest

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“…Epidemiological studies have shown that chronic low levels of NK cell activity is associated with an increased incidence of cancer and NK cell cytotoxicity to be significantly lower in individuals with a high incidence of familial cancer [8, 9]. Reduced levels of circulating NK cell activity in uterine and colorectal cancers were shown to predispose to metastatic dissemination [10, 11]. Most human tumours have very low levels of infiltration by NK cells.…”

Section: Introductionmentioning

confidence: 99%

Natural killer (NK) cell profiles in blood and tumour in women with large and locally advanced breast cancer (LLABC) and their contribution to a pathological complete response (PCR) in the tumour following neoadjuvant chemotherapy (NAC): differential restoration of blood profiles by NAC and surgery

et al. 2015

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BackgroundNK cells contribute to tumour surveillance, inhibition of growth and dissemination by cytotoxicity, secretion of cytokines and interaction with immune cells. Their precise role in human breast cancer is unclear and the effect of therapy poorly studied. The purpose of our study was to characterise NK cells in women with large (≥3 cm) and locally advanced (T3–4, N1–2, M0) breast cancers (LLABCs) undergoing neoadjuvant chemotherapy (NAC) and surgery, and to ascertain their possible contribution to a pathological complete response (pCR).MethodsWomen with LLABCs (n = 25) and healthy female donors [HFDs (n = 10)] were studied. Pathological responses in the breast were assessed using established criteria. Blood samples were collected pre and post NAC and surgery. Flow cytometry and labelled monoclonal antibodies established absolute numbers (AbNs) and percentages (%) of NK cells, and expressing granzyme B/perforin and NKG2D. In vitro NK cytotoxicity was assessed and NK cells and cytokines (IL-2, INF-γ, TGF-β) documented in tumours using immunohistochemical techniques. Data was analysed by SPSS.ResultsWomen with LLABCs had significantly reduced AbNs (160.00 ± 40.00 cells/µl) but not % of NK cells, compared with HFDs (NK: 266.78 ± 55.00 cells/µl; p = 0.020). NAC enhanced the AbN (p = 0.001) and % (p = 0.006) of NK cells in patients with good pathological responses. Granzyme B+/perforin+ cells were significantly reduced (43.41 ± 4.00%), compared with HFDs (60.26 ± 7.00%; p = 0.003). NAC increased the % in good (p = 0.006) and poor (p = 0.005) pathological responders. Pretreatment NK cytotoxicity was significantly reduced in good (37.80 ± 8.05%) and poor (22.80 ± 7.97%) responders (p = 0.001) but remained unchanged following NAC. NK-NKG2D+ cells were unaltered and unaffected by NAC; NKG2D expression was increased in patients with a pCR (p = 0.001). Surgery following NAC was not beneficial, except in those with a pCR. Tumour-infiltrating NK cells were infrequent but increased peritumourally (p = 0.005) showing a significant correlation (p = 0.004) between CD56+ cells and grade of response. Tumour cytokines had no effect.ConclusionWomen with LLABCs have inhibited blood innate immunity, variably reversed by NAC (especially with tumour pCRs), which returned to pretreatment levels following surgery. These and in situ tumour findings suggest a role for NK cells in NAC-induced breast pCR.

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“…Decreased NK cell responses have been detected in patients with lung and liver cancer as well as in melanoma, chronic myeloid and acute lymphoid and myeloid leukemia [43][44][45][46][47] . Another study reported that in patients with metastatic disease, cytotoxic responses of peripheral blood cells against K562 cells were reduced, whereas cancer patients without metastases mounted responses comparable to healthy donors [48] .…”

Section: Nk Cells Within the Tumor Microenvironmentmentioning

confidence: 99%

Natural Killer Cells and Solid Tumors

2011

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Natural killer (NK) cells play an important role in the innate immune response against cancer, in particular in the elimination of tumor metastases and small tumors. NK cell-mediated control of large solid tumors is usually not efficient, although tumors often express high amounts of activating ligands and low levels of inhibitory ligands, such as MHC class I. Thus, we assume that these tumors might be good targets for NK cell-mediated attack. In vitro, NK cells directly kill tumor cells and release soluble factors that affect both innate and adaptive immune responses. To date, in vivo NK cell activation during tumor progression, the influence of the tumor microenvironment on NK cells, and the mechanisms that interfere with their effector function in cancer patients are not completely understood. This review summarizes our current knowledge of NK cells in solid tumors. We will discuss the impact of novel insights into NK cell responses against tumors on the design of NK cell-based therapies.

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Clinical implications of natural killer (NK) cytotoxicity in patients with squamous cell carcinoma of the uterine cervix

Cited by 19 publications

References 9 publications

Natural Killer Cell Activity in Patients with Invasive Cervical Carcinoma: Importance of a Longitudinal Evaluation in Follow-Up

Natural Killer Cell Activity in Patients with Invasive Cervical Carcinoma: Importance of a Longitudinal Evaluation in Follow-Up

Natural killer (NK) cell profiles in blood and tumour in women with large and locally advanced breast cancer (LLABC) and their contribution to a pathological complete response (PCR) in the tumour following neoadjuvant chemotherapy (NAC): differential restoration of blood profiles by NAC and surgery

Natural Killer Cells and Solid Tumors

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