Prognostic value of intratumoral natural killer cells in gastric carcinoma

Ishigami, Sumiya; Natsugoe, Shoji; Tokuda, Koki; Nakajo, Akihiro; Che, Xin; Iwashige, Hirohumi; Aridome, Kuniaki; Hokita, Shuichi; Aikou, Takashi

doi:10.1002/(sici)1097-0142(20000201)88:3<577::aid-cncr13>3.0.co;2-v

Cited by 476 publications

(329 citation statements)

References 15 publications

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“…NKC infiltration, however, did not correlate with either tumour progression or prognosis in this study. NKCs, constituting only a small portion of the tumour-infiltrating lymphocytes (Ishigami et al, 2000b), are components of the innate immune system capable of lysing target cells without prior sensitization (Cooper et al, 2001). Thus, the inability of NKCs to influence the outcome of disease may depend on the low proportion of total cells and weak anticancer specificity of NKCs.…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of immune cell infiltration within gallbladder cancer

et al. 2003

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To investigate the pathophysiological significance of infiltrating antitumour immune cells, we evaluated the quantity of immune cell intratumoral infiltration in 110 surgically resected gallbladder specimens by immunohistochemistry. We examined 45 cases of gallbladder cancer and 65 cases of benign gallbladder diseases for CD4 þ T cells, CD8 þ T cells, natural killer cells (NKCs), and dendritic cells (DCs). High levels of CD4 þ T cell, CD8 þ T cell, NKC, and DC infiltration were recognised in 51.1% (23 out of 45), 37.8% (17 out of 45), 33.3% (15 out of 45), and 48.9% (22 out of 45) of cancer specimens, respectively. High numbers of infiltrating CD4 þ and CD8 þ T cells correlated with decreasing tumour invasion, and high numbers of infiltrating DCs correlated with decreasing lymph-node tumour metastasis. Furthermore, increased infiltration of CD4 þ and CD8 þ T cells and DCs exhibited a significant correlation with prolonged survival. NKC infiltration, however, did not correlate with any of the clinicopathological factors examined. Additionally, high levels of infiltration were not identified in specimens from benign diseases, consistent with the cancerspecific activity of CD4 þ and CD8 þ T cells and DCs. In this study, we demonstrate that CD4 þ and CD8 þ tumour-infiltrating lymphocyte and DCs, but not NKCs, are important factors in the accurate prognosis of survival after surgical removal of gallbladder adenocarcinoma.

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Section: Discussionmentioning

confidence: 99%

Clinical significance of immune cell infiltration within gallbladder cancer

et al. 2003

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“…In addition, baseline intratumoural CD57 did influence on survival. Presence of intratumoral CD57 cells was also associated with favourable survival in studies of colorectal cancer (Coca et al, 1997) and gastric cancer (Ishigami et al, 2000).…”

Section: Discussionmentioning

confidence: 90%

Intratumoural and peripheral blood lymphocyte subsets in patients with metastatic renal cell carcinoma undergoing interleukin-2 based immunotherapy: association to objective response and survival

et al. 2002

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The aim of the present study was to analyse lymphocyte subsets in consecutive peripheral blood samples and consecutive tumour tissue core needle biopsies performed before and during interleukin-2 based immunotherapy, and to correlate the findings with objective response and survival. Twenty-six patients with metastatic renal cell carcinoma were treated with low dose s.c. interleukin-2, interferon-α and histamine. A total of 250 blood samples and 62 core needle biopsies from 23 and 19 of these patients, respectively, were analysed. After 2 weeks of treatment, a significant positive correlation between absolute number of peripheral blood lymphocytes ( P =0.028), CD3 ( P =0.017), CD57 ( P =0.041) and objective response was demonstrated. There was no correlation between any peripheral blood leukocyte subsets and survival. Cytotoxicity of peripheral blood mononuclear cells was not correlated to objective response or survival. Within the tumour tissue at baseline, a significant positive correlation between CD4 ( P =0.027), CD8 ( P =0.028), CD57 ( P =0.007) and objective response was demonstrated. After one month of immunotherapy, a significant positive correlation between intratumoral CD3 ( P =0.026), CD8 ( P =0.015), CD57 ( P =0.009) and objective response was demonstrated. A significant positive correlation between intratumoral baseline CD4 ( P =0.047), baseline CD57 ( P =0.035), CD3 at one month ( P =0.049) and survival was demonstrated. These data provide novel in vivo evidence of the possible contribution of lymphocyte subsets in the tumour reduction in responding patients during interleukin-2 based immunotherapy. Confirmation of the results requires further studies including a larger number of patients. British Journal of Cancer (2002) 87 , 194–201. doi: 10.1038/sj.bjc.6600437 www.bjcancer.com © 2002 Cancer Research UK

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“…Individuals with a high NK cell activity have a reduced risk to develop cancer [121]. Moreover, increased numbers of NK cells in different types of tumors correlate with improved prognosis for cancer patients [2,106,107]. However, emerging evidence exists that NK cell function in the tumor microenvironment becomes impaired during tumor progression.…”

Section: Discussionmentioning

confidence: 99%

“…Functionally, CD57 + NK cells display reduced proliferative capacity, but are potent IFN-γ producers and show high lytic capacity when stimulated via CD16. Thus, high numbers of tumor-infiltrating CD57 + cells were correlated with improved prognosis of cancer patients with several malignancies including lung, gastric and colorectal cancer [2,106,107]. These early observations suggested that CD56 dim CD57 + NK cells might be effective during antitumor responses.…”

Section: Nk Cell Recruitment To the Tumor Sitementioning

confidence: 94%

Shaping of NK Cell Responses by the Tumor Microenvironment

Stojanović

Correia

Cerwenka

2012

Cancer Microenvironment

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Natural killer (NK) cells belong to the innate immune system and are potent cytolytic and cytokineproducing effector cells in response to tumor targets. NK cell based anti-tumor immunotherapy was so far mainly successful in patients with different types of leukemia. For instance, acute myeloid leukemia (AML) patients displayed a prolonged survival if transplanted with haploidentical stem cells giving rise to NK cells with a mismatch in inhibitory killer immunoglobulin receptors (KIRs) and recipients' HLA class I. Although promising results have been achieved with hematological tumors, solid tumors are in most cases poorly controlled by NK cells. Therapeutic protocols that aimed at improving NK cell responses in patients with solid malignancies succeeded in increasing NK cell numbers and functional responses of NK cells isolated from the patients' peripheral blood. However, in the majority of cases tumor progression and overall survival of patients were not significantly improved. There is increasing evidence that tumor-associated NK cells become gradually impaired during tumor progression compared to NK cells from peripheral blood and healthy tissues. Future protocols of NK cell based immunotherapy should integrate three important aspects to improve NK cell anti-tumor activity: facilitating NK cell migration to the tumor site, enhancing their infiltration into the tumor tissue and ensuring subsequent efficient activation in the tumor. This review summarizes the current knowledge of tumor-infiltrating NK cells and the influence of the tumor microenvironment on their phenotype and function.

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Prognostic value of intratumoral natural killer cells in gastric carcinoma

Cited by 476 publications

References 15 publications

Clinical significance of immune cell infiltration within gallbladder cancer

Clinical significance of immune cell infiltration within gallbladder cancer

Intratumoural and peripheral blood lymphocyte subsets in patients with metastatic renal cell carcinoma undergoing interleukin-2 based immunotherapy: association to objective response and survival

Shaping of NK Cell Responses by the Tumor Microenvironment

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