Immune expression in children with Wilms tumor: a pilot study

Holl, Eda K.; Routh, Jonathan C.; Johnston, Ashley W.; Frazier, Victoria; Rice, Henry E.; Tracy, Elizabeth T.; Nair, Smita K.

doi:10.1016/j.jpurol.2019.03.011

Cited by 19 publications

(26 citation statements)

References 41 publications

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“…Similar to other tumors, both adaptive and innate immune cells may infiltrate WT [38][39][40]. However, the relationship between such immune infiltrate and WT cells has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Wilms’ Tumor Primary Cells Display Potent Immunoregulatory Properties on NK Cells and Macrophages

Fiore

Vacca

Tumino

et al. 2021

Cancers

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The immune response plays a crucial defensive role in cancer growth and metastasis and is a promising target in different tumors. The role of the immune system in Wilm’s Tumor (WT), a common pediatric renal malignancy, is still to be explored. The characterization of the immune environment in WT could allow the identification of new therapeutic strategies for targeting possible inhibitory mechanisms and/or lowering toxicity of the current treatments. In this study, we stabilized four WT primary cultures expressing either a blastematous (CD56+/CD133−) or an epithelial (CD56−/CD133+) phenotype and investigated their interactions with innate immune cells, namely NK cells and monocytes. We show that cytokine-activated NK cells efficiently kill WT cells. However, after co-culture with WT primary cells, NK cells displayed an impaired cytotoxic activity, decreased production of IFNγ and expression of CD107a, DNAM-1 and NKp30. Analysis of the effects of the interaction between WT cells and monocytes revealed their polarization towards alternatively activated macrophages (M2) that, in turn, further impaired NK cell functions. In conclusion, we show that both WT blastematous and epithelial components may contribute directly and indirectly to a tumor immunosuppressive microenvironment that is likely to play a role in tumor progression.

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Section: Introductionmentioning

confidence: 99%

Wilms’ Tumor Primary Cells Display Potent Immunoregulatory Properties on NK Cells and Macrophages

Fiore

Vacca

Tumino

et al. 2021

Cancers

View full text Add to dashboard Cite

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“…Moreover, it must be considered that these factors are involved in the inhibition not only of NK cells, but also of other important effectors of anti-tumor response, including T cells and macrophages, that have been detected in the WT microenvironment, mostly confined in the stromal component of the tumor. [10][11][12] Thus, the use of novel therapies interfering with COX-2 and IDO activity may reveal a good strategy to unlock the immune response against WT.…”

Section: Discussionmentioning

confidence: 99%

“…The demonstration that activated NK cells can degranulate upon interaction with str-WT cells adds novel information about the important role that these effectors may play in the immune response against WT. Notably, it has been recently shown that NK cells are present in WT tissues in a significantly high percentage, 10 suggesting that NK cells can be recruited toward WT sites where they can mediate anti-tumor response.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies showed that, compared with normal kidney, WT exhibited infiltration of inflammatory immune cells and overexpression of several inflammatory transcription factors and other inflammatory markers. [10][11][12] Notably, the leucocyte infiltrate was predominantly localized in the stromal component of WT tissue, thus suggesting a preferential attraction of immune cells toward tumor cells displaying an MSC-like phenotype . 12 Different effector cells are involved in immune responses against tumors, including α/β and γ/δ T lymphocytes, and Natural Killer (NK) cells.…”

Section: Introductionmentioning

confidence: 99%

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Stromal-like Wilms tumor cells induce human Natural Killer cell degranulation and display immunomodulatory properties towards NK cells

et al. 2021

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The similarity of stromal-like Wilms tumor (str-WT) cells with mesenchymal stem cells (MSC), suggests their relevant role in the interplay with immune cells in the tumor microenvironment. We investigated the interaction between str-WT cells and NK cells. We observed that str-WT cells expressed some major ligands for activating and inhibitory NK cell receptors. Moreover, they expressed inhibitory checkpoint molecules involved in the negative regulation of anti-tumor immune response. The analysis of the interaction between str-WT cells and NK lymphocytes revealed that activated NK cells could efficiently degranulate upon interaction with str-WT cells. On the other hand, str-WT cells could exert potent inhibitory effects on cytokine-induced activation of NK cell proliferation and phenotype, which were mediated by the production of IDO and PGE2 inhibitory factors. Our data provide insight into the molecular interactions between str-WT cells and NK lymphocytes that may result in different outcomes possibly occurring in the WT microenvironment.

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“…However, not all children are cured and further research is warranted on enhancing the rate of therapeutic efficacy. Holl et al 40 analyzed the immune response of five patients with Wilms’ tumor before undergoing chemotherapy: activated CD8 and CD4 T cells infiltrated the tumor. This indicates that patients with Wilms’ tumor are susceptible to immunotherapy like specific adult malignancies.…”

Section: Discussionmentioning

confidence: 99%

CD8+ T-cell lymphocytes infiltration predict clinical outcomes in Wilms’ tumor

et al. 2020

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The abundance and location of CD8+ tumor-infiltrating lymphocytes demonstrate important facets of the anticancer immune response. CD8-expressing lymphocytes have been used in immunotherapy for multiple cancers. This study aims to determine the association between the abundance and localization of CD8+ tumor-infiltrating lymphocytes and clinical outcomes of Wilms’ tumor. This retrospective study employed 42 pediatric patients diagnosed with Wilms’ tumor. CD8+ tumor-infiltrating lymphocyte counts were calculated based on the mean percentage of stroma occupied by CD8+ lymphocytes at the center and the invasive border of the tumor using immunohistochemistry. CD8+ tumor-infiltrating lymphocyte counts were significantly higher in the center and the invasive border of the early-stage tumor samples. CD8+ tumor-infiltrating lymphocytes in the invasive border and tumor center positively correlated with tumor invasion, regional lymph node invasion, histological type, metastasis, and stage of the tumor. A high CD8+ tumor-infiltrating lymphocyte scores at the invasive margin of the tumor correlated with low tumor recurrence. Low CD8+ tumor-infiltrating lymphocyte scores in the two tumor regions correlated with poor prognosis and shorter disease-free survival. Overall, these findings show that patients with high CD8+ tumor-infiltrating lymphocytes are associated with better clinical outcomes. Therefore, measuring the abundance of CD8+ tumor-infiltrating lymphocytes may be useful in predicting response to cancer immunotherapies.

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Immune expression in children with Wilms tumor: a pilot study

Cited by 19 publications

References 41 publications

Wilms’ Tumor Primary Cells Display Potent Immunoregulatory Properties on NK Cells and Macrophages

Wilms’ Tumor Primary Cells Display Potent Immunoregulatory Properties on NK Cells and Macrophages

Stromal-like Wilms tumor cells induce human Natural Killer cell degranulation and display immunomodulatory properties towards NK cells

CD8+ T-cell lymphocytes infiltration predict clinical outcomes in Wilms’ tumor

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