Digital Immunophenotyping Predicts Disease Free and Overall Survival in Early Stage Melanoma Patients
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...
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MDPI AG
2021-02-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/2/422 |
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| author | Francesco De Logu Francesca Galli Romina Nassini Filippo Ugolini Sara Simi Mara Cossa Clelia Miracco Andrea Gianatti Vincenzo De Giorgi Eliana Rulli Antonio Cossu Daniela Massi Mario Mandalà |
| author_facet | Francesco De Logu Francesca Galli Romina Nassini Filippo Ugolini Sara Simi Mara Cossa Clelia Miracco Andrea Gianatti Vincenzo De Giorgi Eliana Rulli Antonio Cossu Daniela Massi Mario Mandalà |
| author_sort | Francesco De Logu |
| collection | DOAJ |
| description | 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<sup>+</sup> intratumoral T-cells (aHR [100 cell/mm<sup>2</sup> increase] 0.98, 95%CI 0.95–1.00, <i>p</i> = 0.041) and CD163<sup>+</sup> inner peritumoral (aHR [high vs. low] 0.56, 95%CI 0.32–0.99, <i>p</i> = 0.047). A statistically significant longer DFS (aHR [high-high vs. low-low] 0.52, 95%CI 0.28–0.99, <i>p</i> = 0.047) and overall survival (OS) (aHR [high-high vs. low-low] 0.39, 95%CI 0.18–0.85, <i>p</i> = 0.018) was found in patients with a high density of both intratumoral CD8<sup>+</sup> T-cells and CD68<sup>+</sup> macrophages as compared to those with low density of both intratumoral CD8<sup>+</sup> T-cells and CD68<sup>+</sup> macrophages. Consistently, in the validation cohort, patients with high density of both intratumoral CD8<sup>+</sup> and CD3<sup>+</sup> T-cells were associated to a statistically better DFS (aHR[high-high vs. low-low] 0.24, 95%CI 0.10–0.56, <i>p</i> < 0.001) and those with high density of both intratumoral CD8<sup>+</sup> and CD68<sup>+</sup> were associated to a statistically longer OS (aHR[high-high vs. low-low] 0.28, 95%CI 0.09–0.86, <i>p</i> = 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. |
| first_indexed | 2024-03-09T00:48:06Z |
| format | Article |
| id | doaj.art-e9c89533baf84ae6a5b4e105a69e6d5a |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T00:48:06Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-e9c89533baf84ae6a5b4e105a69e6d5a2023-12-11T17:23:38ZengMDPI AGCells2073-44092021-02-0110242210.3390/cells10020422Digital Immunophenotyping Predicts Disease Free and Overall Survival in Early Stage Melanoma PatientsFrancesco De Logu0Francesca Galli1Romina Nassini2Filippo Ugolini3Sara Simi4Mara Cossa5Clelia Miracco6Andrea Gianatti7Vincenzo De Giorgi8Eliana Rulli9Antonio Cossu10Daniela Massi11Mario Mandalà12Section of Clinical Pharmacology and Oncology, Department of Health Sciences, University of Florence, 50100 Florence, ItalyMethodology for Clinical Research Laboratory, Oncology Department, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, ItalySection of Clinical Pharmacology and Oncology, Department of Health Sciences, University of Florence, 50100 Florence, ItalySection of Pathological Anatomy, Department of Health Sciences, University of Florence, 50100 Florence, ItalySection of Pathological Anatomy, Department of Health Sciences, University of Florence, 50100 Florence, ItalyDepartment of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, ItalyUnit of Pathological Anatomy, Department of Medicine, Surgery, and Neurosciences, University of Siena, 53100 Siena, ItalyPathology Unit, Papa Giovanni XXIII Hospital, 24127 Bergamo, ItalyDermatology Unit, University of Florence, 50100 Florence, ItalyMethodology for Clinical Research Laboratory, Oncology Department, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, ItalySection of Pathology, Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, ItalySection of Pathological Anatomy, Department of Health Sciences, University of Florence, 50100 Florence, ItalyDivision of Pathological Anatomy, Papa Giovanni XXIII Hospital, 24127 Bergamo, ItalyBackground: 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<sup>+</sup> intratumoral T-cells (aHR [100 cell/mm<sup>2</sup> increase] 0.98, 95%CI 0.95–1.00, <i>p</i> = 0.041) and CD163<sup>+</sup> inner peritumoral (aHR [high vs. low] 0.56, 95%CI 0.32–0.99, <i>p</i> = 0.047). A statistically significant longer DFS (aHR [high-high vs. low-low] 0.52, 95%CI 0.28–0.99, <i>p</i> = 0.047) and overall survival (OS) (aHR [high-high vs. low-low] 0.39, 95%CI 0.18–0.85, <i>p</i> = 0.018) was found in patients with a high density of both intratumoral CD8<sup>+</sup> T-cells and CD68<sup>+</sup> macrophages as compared to those with low density of both intratumoral CD8<sup>+</sup> T-cells and CD68<sup>+</sup> macrophages. Consistently, in the validation cohort, patients with high density of both intratumoral CD8<sup>+</sup> and CD3<sup>+</sup> T-cells were associated to a statistically better DFS (aHR[high-high vs. low-low] 0.24, 95%CI 0.10–0.56, <i>p</i> < 0.001) and those with high density of both intratumoral CD8<sup>+</sup> and CD68<sup>+</sup> were associated to a statistically longer OS (aHR[high-high vs. low-low] 0.28, 95%CI 0.09–0.86, <i>p</i> = 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.https://www.mdpi.com/2073-4409/10/2/422melanomadigital pathologytumor infiltrating lymphocytes |
| spellingShingle | Francesco De Logu Francesca Galli Romina Nassini Filippo Ugolini Sara Simi Mara Cossa Clelia Miracco Andrea Gianatti Vincenzo De Giorgi Eliana Rulli Antonio Cossu Daniela Massi Mario Mandalà Digital Immunophenotyping Predicts Disease Free and Overall Survival in Early Stage Melanoma Patients Cells melanoma digital pathology tumor infiltrating lymphocytes |
| title | Digital Immunophenotyping Predicts Disease Free and Overall Survival in Early Stage Melanoma Patients |
| title_full | Digital Immunophenotyping Predicts Disease Free and Overall Survival in Early Stage Melanoma Patients |
| title_fullStr | Digital Immunophenotyping Predicts Disease Free and Overall Survival in Early Stage Melanoma Patients |
| title_full_unstemmed | Digital Immunophenotyping Predicts Disease Free and Overall Survival in Early Stage Melanoma Patients |
| title_short | Digital Immunophenotyping Predicts Disease Free and Overall Survival in Early Stage Melanoma Patients |
| title_sort | digital immunophenotyping predicts disease free and overall survival in early stage melanoma patients |
| topic | melanoma digital pathology tumor infiltrating lymphocytes |
| url | https://www.mdpi.com/2073-4409/10/2/422 |
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