Microenvironment in cutaneous melanomas: a gene expression profile study may explain the role of histological regression

Osella‐Abate, Simona; Vignale, Chiara; Annaratone, Laura; Nocifora, Alberto; Bertero, Luca; Castellano, Isabella; Avallone, Gianluca; Conti, Luca; Quaglino, Pietro; Picciotto, Franco; Senetta, Rebecca; Papotti, Mauro; Cassoni, Paola; Ribero, Simone

doi:10.1111/jdv.16784

Cited by 7 publications

(5 citation statements)

References 12 publications

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“…Cutaneous melanomas showing regression revealed lower counts of CD4-positive T reg cells and PD-1-expressing exhausted T cells. On the mRNA level, regressed melanomas showed a higher CD4 and CD8 expression ( 46 ). In addition, a more aggressive phenotype in melanomas was associated with a switch in macrophage polarization from M1 to M2 ( 46 ).…”

Section: Discussionmentioning

confidence: 99%

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Macrophage and T-Cell Infiltration and Topographic Immune Cell Distribution in Non-Melanoma Skin Cancer of the Head and Neck

et al. 2022

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Non-melanoma skin cancer (NMSC) is a heterogeneous tumor entity that is vastly determined by age and UV-light exposure leading to a great mutational burden in cancer cells. However, the success of immune checkpoint blockade in advanced NMSC and the incidence and disease control rates of NMSC in organ transplant recipients compared to immunologically uncompromised patients point toward the emerging importance of the immunologic activity of NMSC. To gain first insight into the role of T-cell and macrophage infiltration in NMSC of the head and neck and capture their different immunogenic profiles, which appear to be highly relevant for the response to immunotherapy, we conducted a whole slide analysis of 107 basal cell carcinoma (BCC) samples and 117 cutaneous squamous cell carcinoma (cSCC) samples. The CD8+ and CD68+ immune cell expression in both cancer types was evaluated by immunohistochemistry and a topographic distribution profile, and the proportion of both cell populations within the two tumor entities was assessed. The results show highly significant differences in terms of CD8+ T-cell and CD68+ macrophage infiltration in BCC and cSCC and indicate cSCC as a highly immunogenic tumor. Yet, BCC presents less immune cell infiltration; the relation between the immune cells compared to cSCC does not show any significant difference. These findings help explain disparities in local aggressiveness, distant metastasis, and eligibility for immune checkpoint blockade in both tumor entities and encourage further research.

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Section: Discussionmentioning

confidence: 99%

“…On the mRNA level, regressed melanomas showed a higher CD4 and CD8 expression ( 46 ). In addition, a more aggressive phenotype in melanomas was associated with a switch in macrophage polarization from M1 to M2 ( 46 ).…”

Section: Discussionmentioning

confidence: 99%

Macrophage and T-Cell Infiltration and Topographic Immune Cell Distribution in Non-Melanoma Skin Cancer of the Head and Neck

et al. 2022

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“…However, risk tools (such as those at melanomarisk.org.au) have been developed based on multiple risk factors that help predict recurrence 17 and the development of subsequent primary melanoma 18 and can be used to tailor surveillance accordingly. The role of somatic genetic mutations and gene expression profiles of primary melanomas, 19 as well as the detection of circulating tumour DNA need further investigation. Further high-quality research is needed on the effectiveness and cost-effectiveness of different surveillance strategies to guide evidence-based decision-making for optimal patient care.…”

Section: Surveillance Of Patients With Thin Melanomamentioning

confidence: 99%

Surveillance of patients with thin melanoma

Ribero

Cust

2021

Aust J Dermatology

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“…To guide clinical decisions, further validation of candidate predictive biomarkers is warranted. [14][15][16] Most of the available data on CTLA-4 expression are limited to human T cells. However, the detection of the CTLA-4 protein in various cells other than T lymphocytes suggests its involvement not only in the established classical mechanism regulating T lymphocyte activity but also in the modulation of functions in other immunocompetent cells.…”

Section: Introductionmentioning

confidence: 99%

The Cytomorphology of Melanoma with a Special Emphasis on the Immune Checkpoint Proteins CTLA-4, PD-1, and PD-L1

Tiemann,

Samoilova,

Atiakshin

et al. 2023

Nature Cell and Science

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Background and objectives:The development of therapeutic anti-PD-1/PD-L1/CTLA-4 monoclonal antibodies, leading to the reactivation of a specific antitumor immune response, has emerged as a promising strategy for immunotherapy in various cancers, including melanoma. Given the complexity of the tumor microenvironment and the dynamic interaction between tumors and immune cells, a better understanding of the PD-1/PD-L1/CTLA-4 regulatory pathways in tumors is required. Methods:To address this issue, we performed immunophenotyping of CTLA4/PD1/PD-L1-positive cells in melanoma via multiple immunofluorescent immunolabeling. Primary antibodies against PD-1, PD-L1, and CTLA-4, along with a panel of CD antibodies targeting various cell types (CD1a, CD3, CD8, and CD68), were utilized for immunolabelling. Tyramide signal amplification (TSA) was used to visualize bound primary anti-CTLA-4 antibodies derived from four different clones. To simultaneously detect antigens from the same host species, TSA with subsequent heat elution was performed after each immunostaining step.Results: CTLA-4 and PD-L1 were not expressed in malignant cells in melanoma but were observed in the tumor microenvironment; especially in tumor-associated inflammatory cells such as macrophages and dendritic cells. Moreover, we found that CTLA-4 expression was not limited to T lymphocytes. Conclusions:The detection of CTLA-4 in various cells other than T lymphocytes suggests the participation of this molecule in regulating T lymphocyte activity beyond the well-known classical scheme. The expansion of the existing ideas regarding the role of CTLA-4 may lead to the development of new approaches for improving diagnostic accuracy. Additionally, these findings suggest that CTLA-4 has more widespread effects on immune regulation.

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Microenvironment in cutaneous melanomas: a gene expression profile study may explain the role of histological regression

Cited by 7 publications

References 12 publications

Macrophage and T-Cell Infiltration and Topographic Immune Cell Distribution in Non-Melanoma Skin Cancer of the Head and Neck

Macrophage and T-Cell Infiltration and Topographic Immune Cell Distribution in Non-Melanoma Skin Cancer of the Head and Neck

Surveillance of patients with thin melanoma

The Cytomorphology of Melanoma with a Special Emphasis on the Immune Checkpoint Proteins CTLA-4, PD-1, and PD-L1

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