NK cells sense tumors, course of disease and treatments

Fregni, Giulia; Perier, Aurélie; Avril, Marie-Françoise; Caignard, Anne

doi:10.4161/onci.1.1.18312

Cited by 38 publications

(51 citation statements)

References 75 publications

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“…Romagnani and colleagues previously showed that lymph node could be the site of NK cell final maturation during the course of an immune reaction and resident CD56 bright NK cells from paracortical/ follicular hyperplasic lymph node may acquire CD16 and KIR and recirculate in the blood (31). It is interesting to note that our data indicate different regulation of NK receptors in CD16 but that NKp46 was correlated with NKG2D (21,23,32 Immunotherapy may be considered as a complementary approach that can be integrated in therapeutic strategies at different stages of the disease. In patients with metastatic melanoma, blocking immune checkpoint of T-cell activation with specific mAbs (anti-CTLA4 and anti-PD1) is a promising issue to restore efficient antitumor immune response.…”

Section: Discussioncontrasting

confidence: 45%

Mature Cytotoxic CD56bright/CD16+Natural Killer Cells Can Infiltrate Lymph Nodes Adjacent to Metastatic Melanoma

et al. 2014

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Melanomas are characterized by high metastatic potential, with regional lymph node representing the most frequent site of early dissemination in this disease. These regional lymph nodes also represent the primary site for differentiation of natural killer (NK) cells. Although blood-derived NK cells can efficiently lyse melanoma cells isolated from metastatic lymph node (M-LN), there has been no study of the properties of the most disease-relevant NK cells isolated from M-LN in patients with melanoma. Here, we report that M-LN contains 0.5% to 11% of CD56 bright NK cells among CD45 þ hematopoietic cells present and that this cell

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Section: Discussioncontrasting

confidence: 45%

Mature Cytotoxic CD56bright/CD16+Natural Killer Cells Can Infiltrate Lymph Nodes Adjacent to Metastatic Melanoma

et al. 2014

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“…Compared with blood NK cells, only a limited amount of information is available on tissue infiltrating NK-TILs in breast cancer (Jochems and Schlom, 2011), which usually present more severe phenotypic and functional alterations compared with circulating or non-cancerous tissue-infiltrating NK counterparts (Fregni et al, 2012). Although the number of NK cells coming into contact with neoplastic cells constitute a small percentage of the infiltrating lymphocytes, they can play an important role in the prognosis of tumors (Stojanovic and Cerwenka, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Correlation between NK cell infiltrates and prognosis has been reported in various tumors. However, tumor-infiltrating NK cells are yet poorly characterized (Fregni et al, 2012). Mamessier et al (2011) have shown that breast tumor progression involves NK cell dysfunction and that breast tumors mold their environment to evade NK cell anti-tumor immunity.…”

Section: Introductionmentioning

confidence: 99%

Is the Tumor Infiltrating Natural Killer Cell (NK-TILs) Count in Infiltrating Ductal Carcinoma of Breast Prognostically Significant?

Rathore

Goel²,

Makker³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Asian Pac J Cancer Prev, 15 (8), 3757-3761 IntroductionBreast cancer is the most common cause of cancer death in women worldwide (Key et al., 2001), and represents the leading or second most leading cancer in females in India (Ferlay et al., 2010;D'Souza et al., 2013a;2013b). Currently, two major challenges of breast cancer research are; to understand the interrelation between breast cancer and anti-tumor immunity, and to identify candidates whose targeting would contribute to enhance anti-tumor efficiency (Mamessier et al., 2012).The cancer tissue is invaded by a mixed population of immune cells, including T-cells, B-cells, natural killer (NK) cells and macrophages. For a long time NK cells were considered merely as relatively primitive killers, but now they are seen not only as bonafide actors in innate immunity but are also important cells that shape and influence the adaptive immune responses (Poli et al., 2009). NK cells are effector lymphocytes of innate immune system that act by limiting the growth and dissemination of the tumor and are known to have an immunoregulatory role.An established marker for NK cells, CD56, is an AbstractPurpose: The aim of this study was to investigate the prognostic significance of the CD56+NK-TIL count in infiltrating ductal carcinoma (IDC) of breast. Material and Methods: Immunohistochemistry (IHC) was performed using antibodies specific for CD56 on formalin-fixed and paraffin-embedded tissue sections of 175 infiltrating ductal carcinomas (IDC) of breast. Distribution of intratumoral and stromal CD56+NK-TILs was assessed semi-quantitatively. Results: A low intratumoral CD56+count showed significant and inverse associations with tumor grade, stage, and lymph node status, whereas it had significant and direct association with response to treatment indicating good prognosis. These patients had better survival (χ 2 =4.80, p<0.05) and 0.52 fold lower death rate (HR=0.52, 95% CI=0.28-0.93) as compared to patients with high CD56+ intratumoral count. The association of survival was insignificant with low CD56 stromal count as compared to high CD56 stromal count (χ 2 =1.60, p>0.05). Conclusion: To conclude, although NK-TIL count appeared as a significant predictor of prognosis, it alone may not be sufficient for predicting the outcome considering the fact that there exists a crosstalk between NK-TILs and the other immune infiltrating TILs.

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“…15 In addition, chemotherapy treated patients displayed distinct phenotypic modulations, 24 indicating that tumor progression and conventional chemotherapy may interfere with NK cell status in melanoma patients. 25 In a recent study, comparing tumor positive and tumor-free Sentinel lymph nodes (SLN), we found that more numerous cytotoxic cells (CD8 C cells, Granzyme C cells, NK cells) infiltrated tumor-free SLN. We also found that NK cells in SLN correlated with higher rate of relapses, supporting a tumor-promoting role of NK cells in SLN.…”

Section: Discussionmentioning

confidence: 99%

NKp30 isoforms and NKp46 transcripts in metastatic melanoma patients: Unique NKp30 pattern in rare melanoma patients with favorable evolution

et al. 2016

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Given the NK cell-based immunosurveillance of melanoma, we investigated the prognostic value of NKp46 transcript and NKp30 isoform (NKp30A, NKp30B and NKp30C) profiling in blood of 187 melanoma patients including 13 long survivors (LS), metastatic patients that have controlled the disease. Compared to healthy volunteers (HV), patients had reduced amounts of transcripts of the three NKp30 isoforms (NKp30 A, B and C) but similar ratios between NKp30 isoforms (DAB, DAC, DBC). Stratification of patients according to disease stage showed higher NKp30C and lower NKp46 transcripts in stage IV patients. Furthermore, patients with previous history of conventional chemotherapy displayed reduced NKp30A transcripts. The expression levels of NKp30 isoforms failed to predict survival from sampling of patients, while NKp46 expression predicted melanoma outcome. LS patients displayed elevated NKp30A levels, accordingly high DAB and DBC ratios, and a unique pattern of rare allelic variants of NKp30 SNPs. Moreover, NK cells from LS displayed correlated NKp30/NKp46 membrane expression, high spontaneous and NKp30-or NKp46-triggered degranulation. These data outline the impact of NKp30 and NKp46 transcripts on melanoma evolution and identify unique genetic features of NKp30 associated with higher NK activation in rare LS melanoma patients that control a metastatic disease.

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NK cells sense tumors, course of disease and treatments

Cited by 38 publications

References 75 publications

Mature Cytotoxic CD56bright/CD16+Natural Killer Cells Can Infiltrate Lymph Nodes Adjacent to Metastatic Melanoma

Mature Cytotoxic CD56bright/CD16+Natural Killer Cells Can Infiltrate Lymph Nodes Adjacent to Metastatic Melanoma

Is the Tumor Infiltrating Natural Killer Cell (NK-TILs) Count in Infiltrating Ductal Carcinoma of Breast Prognostically Significant?

NKp30 isoforms and NKp46 transcripts in metastatic melanoma patients: Unique NKp30 pattern in rare melanoma patients with favorable evolution

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