Next Article in Journal
MicroRNA-27b-3p Targets the Myostatin Gene to Regulate Myoblast Proliferation and Is Involved in Myoblast Differentiation
Next Article in Special Issue
Predictive and Prognostic Molecular Factors in Diffuse Large B-Cell Lymphomas
Previous Article in Journal
Zebrafish Models of Autosomal Dominant Ataxias
Previous Article in Special Issue
Immune Infiltrates in Breast Cancer: Recent Updates and Clinical Implications
 
 
Article

Digital Immunophenotyping Predicts Disease Free and Overall Survival in Early Stage Melanoma Patients

1
Section of Clinical Pharmacology and Oncology, Department of Health Sciences, University of Florence, 50100 Florence, Italy
2
Methodology for Clinical Research Laboratory, Oncology Department, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy
3
Section of Pathological Anatomy, Department of Health Sciences, University of Florence, 50100 Florence, Italy
4
Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
5
Unit of Pathological Anatomy, Department of Medicine, Surgery, and Neurosciences, University of Siena, 53100 Siena, Italy
6
Pathology Unit, Papa Giovanni XXIII Hospital, 24127 Bergamo, Italy
7
Dermatology Unit, University of Florence, 50100 Florence, Italy
8
Section of Pathology, Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, Italy
9
Division of Pathological Anatomy, Papa Giovanni XXIII Hospital, 24127 Bergamo, Italy
10
Unit of Medical Oncology, University of Perugia, 06123 Perugia, Italy
*
Authors to whom correspondence should be addressed.
FDL and FG shared first Authorship and equally contributed to the study.
DM and MM shared last Authorship and equally contributed to the study.
Academic Editors: Shikhar Mehrotra and Anna Sapino
Cells 2021, 10(2), 422; https://doi.org/10.3390/cells10020422
Received: 13 January 2021 / Revised: 2 February 2021 / Accepted: 10 February 2021 / Published: 17 February 2021
(This article belongs to the Special Issue Identification of Prognostic Markers in Cancer Biology)
Background: the prognostic significance of tumor infiltrating lymphocytes (TILs) in intermediate/thick primary cutaneous melanoma (PCM) remains controversial, partially because conventional evaluation is not reliable, due to inter-observer variability and diverse scoring methods. We aimed to assess the prognostic impact of the density and spatial distribution of immune cells in early stage intermediate/thick PCM. Materials and Methods: digital image acquisition and quantitative analysis of tissue immune biomarkers (CD3, CD4, CD8, CD68, PD-L1, CD163, FOX-P3, and PD-1) was carried out in a training cohort, which included patients with primary PCM ≥ 2 mm diagnosed, treated, and followed-up prospectively in three Italian centers. Results were validated in an independent Italian cohort. Results: in the training cohort, 100 Stage II–III melanoma patients were valuable. At multivariable analysis, a longer disease free survival (DFS) was statistically associated with higher levels of CD4+ intratumoral T-cells (aHR [100 cell/mm2 increase] 0.98, 95%CI 0.95–1.00, p = 0.041) and CD163+ inner peritumoral (aHR [high vs. low] 0.56, 95%CI 0.32–0.99, p = 0.047). A statistically significant longer DFS (aHR [high-high vs. low-low] 0.52, 95%CI 0.28–0.99, p = 0.047) and overall survival (OS) (aHR [high-high vs. low-low] 0.39, 95%CI 0.18–0.85, p = 0.018) was found in patients with a high density of both intratumoral CD8+ T-cells and CD68+ macrophages as compared to those with low density of both intratumoral CD8+ T-cells and CD68+ macrophages. Consistently, in the validation cohort, patients with high density of both intratumoral CD8+ and CD3+ T-cells were associated to a statistically better DFS (aHR[high-high vs. low-low] 0.24, 95%CI 0.10–0.56, p < 0.001) and those with high density of both intratumoral CD8+ and CD68+ were associated to a statistically longer OS (aHR[high-high vs. low-low] 0.28, 95%CI 0.09–0.86, p = 0.025). Conclusion: our findings suggest that a specific preexisting profile of T cells and macrophages distribution in melanomas may predict the risk of recurrence and death with potential implications for the stratification of stage II–III melanoma patients. View Full-Text
Keywords: melanoma; digital pathology; tumor infiltrating lymphocytes melanoma; digital pathology; tumor infiltrating lymphocytes
Show Figures

Figure 1

MDPI and ACS Style

De Logu, F.; Galli, F.; Nassini, R.; Ugolini, F.; Simi, S.; Cossa, M.; Miracco, C.; Gianatti, A.; De Giorgi, V.; Rulli, E.; Cossu, A.; Massi, D.; Mandalà, M. Digital Immunophenotyping Predicts Disease Free and Overall Survival in Early Stage Melanoma Patients. Cells 2021, 10, 422. https://doi.org/10.3390/cells10020422

AMA Style

De Logu F, Galli F, Nassini R, Ugolini F, Simi S, Cossa M, Miracco C, Gianatti A, De Giorgi V, Rulli E, Cossu A, Massi D, Mandalà M. Digital Immunophenotyping Predicts Disease Free and Overall Survival in Early Stage Melanoma Patients. Cells. 2021; 10(2):422. https://doi.org/10.3390/cells10020422

Chicago/Turabian Style

De Logu, Francesco, Francesca Galli, Romina Nassini, Filippo Ugolini, Sara Simi, Mara Cossa, Clelia Miracco, Andrea Gianatti, Vincenzo De Giorgi, Eliana Rulli, Antonio Cossu, Daniela Massi, and Mario Mandalà. 2021. "Digital Immunophenotyping Predicts Disease Free and Overall Survival in Early Stage Melanoma Patients" Cells 10, no. 2: 422. https://doi.org/10.3390/cells10020422

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop