Immunoplasticity in cutaneous melanoma: beyond pure morphology

Bosisio, Francesca Maria

doi:10.1007/s00428-016-2058-y

Cited by 3 publications

(2 citation statements)

References 117 publications

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“…A host immune response is observed on a regular basis in melanocytic neoplasms with infiltration of the lesion by tumour‐infiltrating leucocytes (TILs), i.e. lymphocytes, that may result in elimination of part or all of the melanocytic lesion 11‐13 . In benign melanocytic lesions a strong inflammatory response with immunologically mediated rejection of the naevus cells and circumferential depigmentation of surrounding keratinocytes is known as the ‘halo phenomenon’, and eponymous for halo naevi (HN) 7 .…”

Section: Introductionmentioning

confidence: 99%

“…While the host response, including the immunogenic environment (particularly T lymphocytes and macrophages), has been extensively studied in conventional primary cutaneous melanoma, 10,12,15,17–21 the host response with the immunogenic environment in spitzoid melanocytic neoplasms remains largely elusive. In particular, the character of infiltrating T lymphocytes is unknown.…”

Section: Introductionmentioning

confidence: 99%

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Integrative histopathological and immunophenotypical characterisation of the inflammatory microenvironment in spitzoid melanocytic neoplasms

et al. 2020

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Aims The role of inflammation in conventional cutaneous melanoma has been extensively studied, whereas only little is known about the inflammatory microenvironment and immunogenic properties of spitzoid melanocytic neoplasms. The composition of infiltrating immune cells and the architectural distribution of the inflammation, in particular, are still obscure. This is the first study, to our knowledge, to systematically characterise the inflammatory patterns and the leucocyte subsets in spitzoid melanocytic lesions. Methods and results We examined 79 spitzoid neoplasms including banal Spitz naevi (SN, n = 50), atypical Spitz tumours (AST, n = 17) and malignant Spitz tumours (MST, n = 12) using histopathological analysis and immunohistochemistry. Spitzoid melanocytic lesions showed a high frequency (67.1%, n = 53 of 79) of inflammation. Four inflammatory patterns were identified according to architectural composition, distribution and intensity of inflammation. The majority of the inflammatory infiltrate corresponded to CD3+/CD8+ T lymphocytes (56.1%), followed by CD3+/CD4+ T cells (35.7%) and CD68+ histiocytes (20.3%). CD3+/TIA‐1+ cytotoxic T lymphocytes constituted 3.7% of inflammatory cells. Rarely, CD3+/ granzyme B+ cytotoxic T lymphocytes (2.7%) and CD138+ plasma cells (0.5%) were detected in the infiltrating immune cells. There was no significant difference in the inflammatory cellular composition among the spitzoid melanocytic subgroups (SN versus AST versus MST). Conclusion Our findings demonstrate that Spitz tumours are highly immunogenic lesions. Inflammation with the presence of lymphocytic aggregates predominated in SN, but was not distinctive for this melanocytic category. A strong and intense inflammation was suggestive of an underlying malignancy. The infiltrating cytotoxic T lymphocyte subsets in Spitz tumours deserve further investigation in larger study cohorts to elucidate prognostic and immuno‐oncological therapeutic relevance.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Integrative histopathological and immunophenotypical characterisation of the inflammatory microenvironment in spitzoid melanocytic neoplasms

et al. 2020

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Functional heterogeneity of lymphocytic patterns in primary melanoma dissected through single-cell multiplexing

Bosisio

Antoranz²,

Bolognesi

et al. 2018

Preprint

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1In melanoma, the lymphocytic infiltrate is a prognostic parameter classified morphologically into "brisk", 2 "non-brisk" and "absent" entailing a functional association that has never been proved. Recently, it has been 3shown that lymphocytic populations can be very heterogeneous, and that anti-PD-1 immunotherapy 4 supports activated T cells. Here, we characterize the immune landscape in primary melanoma by high-5dimensional single cell multiplex analysis in tissue sections (MILAN technique) followed by image analysis, 6RT-PCR and shotgun proteomics. We observed that the brisk and non-brisk patterns are heterogeneous 7 functional categories that can be further sub-classified into active, transitional or exhausted. The 8 classification of primary melanomas based on the functional paradigm also shows correlation with 9 spontaneous regression, and an improved prognostic value than that of the brisk classification. Finally, the 10 main inflammatory cell subpopulations that are present in the microenvironment associated with activation 11 and exhaustion and their spatial relationships are described using neighbourhood analysis. 12

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Functional heterogeneity of lymphocytic patterns in primary melanoma dissected through single-cell multiplexing

Bosisio

Antoranz

Herck

et al. 2020

eLife

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In melanoma, the lymphocytic infiltrate is a prognostic parameter classified morphologically into ‘brisk’, ‘non-brisk’ and ‘absent’ entailing a functional association that has never been proved. Recently, it has been shown that lymphocytic populations can be very heterogeneous, and that anti-PD-1 immunotherapy supports activated T cells. Here, we characterize the immune landscape in primary melanoma by high-dimensional single-cell multiplex analysis in tissue sections (MILAN technique) followed by image analysis, RT-PCR and shotgun proteomics. We observed that the brisk and non-brisk patterns are heterogeneous functional categories that can be further sub-classified into active, transitional or exhausted. The classification of primary melanomas based on the functional paradigm also shows correlation with spontaneous regression, and an improved prognostic value when compared to that of the brisk classification. Finally, the main inflammatory cell subpopulations that are present in the microenvironment associated with activation and exhaustion and their spatial relationships are described using neighbourhood analysis.

show abstract

Immunoplasticity in cutaneous melanoma: beyond pure morphology

Cited by 3 publications

References 117 publications

Integrative histopathological and immunophenotypical characterisation of the inflammatory microenvironment in spitzoid melanocytic neoplasms

Integrative histopathological and immunophenotypical characterisation of the inflammatory microenvironment in spitzoid melanocytic neoplasms

Functional heterogeneity of lymphocytic patterns in primary melanoma dissected through single-cell multiplexing

Functional heterogeneity of lymphocytic patterns in primary melanoma dissected through single-cell multiplexing

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