The role of αβ T-cells in spontaneous regression of melanoma tumors in swine

Čížková, Jana; Šinkorová, Zuzana; Strnadova, Kristyna; Červinková, Monika; Horák, Vratislav; Sinkora, J; Štěpánová, Kateřina; Šinkora, Marek

doi:10.1016/j.dci.2018.10.001

Cited by 19 publications

(10 citation statements)

References 31 publications

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“…Here we found that CD21 expression on B cells correlated with the serum total IgG levels. Interestingly, Cizkova et al also found an increase of melanoma-associated DP T lymphocytes in peripheral blood during melanoma regression at adult stages (43). In our study, we showed a higher proportion of this T cell subset already in young pigs.…”

Section: Discussionsupporting

confidence: 72%

The Composition of Circulating Leukocytes Varies With Age and Melanoma Onset in the MeLiM Pig Biomedical Model

et al. 2020

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Immunological research in pigs benefits from many improvements with a direct impact on the veterinary control of pig husbandry and on biomedical models. We compiled the available knowledge to develop gating strategies to monitor simultaneously all blood immune cell types by multicolor flow cytometry in Melanoblastoma-bearing Libechov Minipigs (MeLiM). The MeLiM pig spontaneously develops cutaneous melanomas that regress few months later. We monitored lymphoid and myeloid cell subsets in 3 to 21 weeks old pigs. Interestingly, neutrophils, type III monocytes (CD163 + CD14 + MHC II −) and CD4 − CD8α − T cells are less abundant in oldest animals in contrast to eosinophils, type II monocytes (CD163 − CD14 low MHC II +), B cells, γδ T cells, CD4 + CD8α + and CD4 − CD8α + T cells. Melanoma occurrence led to changes in the blood cell composition. Higher proportions of NK cells, CD4 + and CD4 + CD8α + T cells, and CD21 − B cells among B cells are found in young melanoma-bearing piglets, consistent with the immune-mediated spontaneous regression in the MeLiM model.

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Section: Discussionsupporting

confidence: 72%

The Composition of Circulating Leukocytes Varies With Age and Melanoma Onset in the MeLiM Pig Biomedical Model

et al. 2020

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“…Spontaneous regression in both the Sinclair miniature swine and the MeLiM melanomas represents a promising immunological model for monitoring immune cells participating in anti-melanoma reaction. Double-positive (DP) T-lymphocyte (CD4 + /CD8 high ) populations of effector/memory T-cells [both in the peripheral blood (PBL) and within the tumour (TIL)] have been reported to expand in MeLiM animals during melanoma regression and it is postulated that they are involved in the regression process [91]. This contrasts with the Sinclair miniature swine model, in which populations of DP lymphocytes were generally consistent in all TIL and PBL populations examined [92].…”

Section: Melanoma-bearing Libechov Minipigmentioning

confidence: 99%

Spontaneously occurring melanoma in animals and their relevance to human melanoma

Weyden

Brenn

Patton

et al. 2020

The Journal of Pathology

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In contrast to other cancer types, melanoma incidence has been increasing over the last 50 years, and while it still represents less than 5% of all cutaneous malignancies, melanoma accounts for the majority of skin cancer deaths, due to its propensity to metastasise. Whilst melanoma most commonly affects the skin, it can also arise in mucosal surfaces, the eye, and the brain. For new therapies to be developed, a better understanding of the genetic landscape, signalling pathways, and tumour–microenvironmental interactions is needed. This is where animal models are of critical importance. The mouse is the foremost used model of human melanoma. Arguably this is due to its plethora of benefits as a laboratory animal; however, it is important to note that unlike humans, melanocytes are not present at the dermal–epidermal junction in mice and mice do not develop melanoma without genetic manipulation. In contrast, there are numerous reports of animals that spontaneously develop melanoma, ranging from sharks and parrots to hippos and monkeys. In addition, several domesticated and laboratory‐bred animals spontaneously develop melanoma or UV‐induced melanoma, specifically, fish, opossums, pigs, horses, cats, and dogs. In this review, we look at spontaneously occurring animal ‘models’ of melanoma and discuss their relevance to the different types of melanoma found in humans. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland..

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“…Flow cytometry revealed two DP T-lymphocyte subpopulations, i.e., melanoma-associated CD4 + /CD8 high T-lymphocytes in peripheral blood and CD4 + /CD8 high TILs in melanoma tissue (together with CD4 − /CD8 + T-lymphocytes), which expanded during melanoma regression. They showed a similar expression of selected CD markers between different pigs and different melanoma loci among the same pig, suggesting that they are effector/memory αβ T-cells considerably involved in spontaneous regression of MeLiM melanoma [235]. It is important to mention, that CD4 + /CD8 + cells are more frequent in pigs, reaching up to 60% of total T-cell counts in adult pig blood, in contrast to 3% in human [236].…”

Section: The Melanoma-bearing Libechov Minipigmentioning

confidence: 99%

“…Nonetheless, MeLiM peripheral DP cells differ in the intensity of CD8 expression, with CD8 high expression in the melanoma-bearing animals in later stages of tumor regression compared to CD8 low positivity in their melanoma-free littermates (both groups at the age of eight months). Importantly, a unique DP cell subpopulation was identified in the blood of regressive MeLiM animals, representing one T-cell clone carrying a mono-specific TCRβ receptor, which is supposed to be responsible for melanoma regression [235]. Our unpublished data about cytokine production of DP T-cells suggest that these cells represent a non-naïve (activated, recirculating) lymphocyte subpopulation with immunomodulatory activity.…”

Section: The Melanoma-bearing Libechov Minipigmentioning

confidence: 99%

Melanoma-Bearing Libechov Minipig (MeLiM): The Unique Swine Model of Hereditary Metastatic Melanoma

Horák

Palanová

Čížková

et al. 2019

Genes

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National cancer databases document that melanoma is the most aggressive and deadly cutaneous malignancy with worldwide increasing incidence in the Caucasian population. Around 10% of melanomas occur in families. Several germline mutations were identified that might help to indicate individuals at risk for preventive interventions and early disease detection. More than 50% of sporadic melanomas carry mutations in Ras/Raf/mitogen-activated protein kinase (MAPK/MEK) pathway, which may represent aims of novel targeted therapies. Despite advances in targeted therapies and immunotherapies, the outcomes in metastatic tumor are still unsatisfactory. Here, we review animal models that help our understanding of melanoma development and treatment, including non-vertebrate, mouse, swine, and other mammal models, with an emphasis on those with spontaneously developing melanoma. Special attention is paid to the melanoma-bearing Libechov minipig (MeLiM). This original swine model of hereditary metastatic melanoma enables studying biological processes underlying melanoma progression, as well as spontaneous regression. Current histological, immunohistochemical, biochemical, genetic, hematological, immunological, and skin microbiome findings in the MeLiM model are summarized, together with development of new therapeutic approaches based on tumor devitalization. The ongoing study of molecular and immunological base of spontaneous regression in MeLiM model has potential to bring new knowledge of clinical importance.

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The role of αβ T-cells in spontaneous regression of melanoma tumors in swine

Cited by 19 publications

References 31 publications

The Composition of Circulating Leukocytes Varies With Age and Melanoma Onset in the MeLiM Pig Biomedical Model

The Composition of Circulating Leukocytes Varies With Age and Melanoma Onset in the MeLiM Pig Biomedical Model

Spontaneously occurring melanoma in animals and their relevance to human melanoma

Melanoma-Bearing Libechov Minipig (MeLiM): The Unique Swine Model of Hereditary Metastatic Melanoma

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