Absence of multinucleated giant cell reaction as an indicator of tumor progression in oral tongue squamous cell carcinoma

Medeiros, Vanessa Alves de; Santos, Hellen Bandeira de Pontes; Monteiro, Bárbara Vanessa de Brito; Paz, Alexandre Rolim da; Alves, Pollianna Muniz; Nonaka, Cassiano Francisco Weege

doi:10.1007/s00405-021-07139-z

Cited by 2 publications

(3 citation statements)

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“…However, they have been observed at high frequency in squamous cell carcinomas of multiple tissues 57 and papillary thyroid carcinomas 58 . They can either be correlated with good 57 or poor prognosis 58 depending on the tumour type and in vitro studies have associated MGCs with increased capacity for complement-mediated phagocytosis of large targets and amyloid deposits 55 . In Znrf3 cKO adrenals, MGCs are characterised by high levels of CD68, F4/80, MERTK, TYROBP and TREM2 expression and drastically reduced expression of IBA-1 (Fig 2G-I & Fig S4C-D).…”

Section: Discussionmentioning

confidence: 99%

“…Literature on their association with tumours is rather scarce. However, they have been observed at high frequency in squamous cell carcinomas of multiple tissues 57 and papillary thyroid carcinomas 58 . They can either be correlated with good 57 or poor prognosis 58 depending on the tumour type and in vitro studies have associated MGCs with increased capacity for complement-mediated phagocytosis of large targets and amyloid deposits 55 concomitant with regression of hyperplasia and are maintained up to 78 weeks.…”

Section: Discussionmentioning

confidence: 99%

“…However, they have been observed at high frequency in squamous cell carcinomas of multiple tissues 57 and papillary thyroid carcinomas 58 . They can either be correlated with good 57 or poor prognosis 58 depending on the tumour type and in vitro studies have associated MGCs with increased capacity for complement-mediated phagocytosis of large targets and amyloid deposits 55 concomitant with regression of hyperplasia and are maintained up to 78 weeks. In contrast, they only appear at late stages in females, are less frequent than in males and are mostly found associated with indolent non-metastatic lesions at 78 weeks.…”

Section: Discussionmentioning

confidence: 99%

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Sexually dimorphic activation of innate antitumour immunity prevents adrenocortical carcinoma development

Wilmouth

Olabe

Garcia-Garcia

et al. 2022

Preprint

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SummaryIn contrast with most cancers, adrenocortical carcinomas (ACC) are more frequent in women than men, but the underlying mechanisms of this sexual dimorphism remain elusive. Homozygous deletion of the negative WNT pathway regulator ZNRF3 is the most frequent alteration in ACC patients. Here, we show that Cre-mediated inactivation of Znrf3 in steroidogenic cells of the mouse adrenal cortex is associated with sexually dimorphic tumour progression. Indeed, although most knockout female mice develop metastatic carcinomas over an 18 month-time course, adrenal hyperplasia gradually regresses in male knockout mice. This male-specific regression is associated with induction of senescence and recruitment of macrophages, which differentiate as active phagocytes that clear-out senescent preneoplastic cells. Macrophage recruitment is also observed in female mice. However, it is delayed and dampened compared to males, which allows for tumour progression. Interestingly, testosterone treatment of female knockouts is sufficient to induce senescence, recruitment of phagocytic macrophages and regression of hyperplasia. We further show that although macrophages are present within adrenal tumours at 18 months, MERTKhigh active phagocytes are mostly found in indolent lesions in males but not in aggressive tumours in females. Consistent with our observations in mice, analysis of RNA sequencing data from the TCGA cohort of ACC shows that phagocytic macrophages are more prominent in men than women and associated with better prognosis. Altogether, these data establish that phagocytic macrophages prevent aggressive ACC development in male mice and suggest that they may play a key role in the unusual sexual dimorphism of ACC in patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…However, they have been observed at high frequency in squamous cell carcinomas of multiple tissues 57 and papillary thyroid carcinomas 58 . They can either be correlated with good 57 or poor prognosis 58 depending on the tumour type and in vitro studies have associated MGCs with increased capacity for complement-mediated phagocytosis of large targets and amyloid deposits 55 concomitant with regression of hyperplasia and are maintained up to 78 weeks. In contrast, they only appear at late stages in females, are less frequent than in males and are mostly found associated with indolent non-metastatic lesions at 78 weeks.…”

Section: Discussionmentioning

confidence: 99%

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