scholarly journals Circulating CD8 + mucosal‐associated invariant T cells correlate with improved treatment responses and overall survival in anti‐PD‐1‐treated melanoma patients

2022 ◽  
Vol 11 (1) ◽  
Author(s):  
Victoria M Vorwald ◽  
Dana M Davis ◽  
Robert J Van Gulick ◽  
Robert J Torphy ◽  
Jessica SW Borgers ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cells ◽  
Melanoma Patients ◽  
Invariant T Cells ◽  
Treatment Responses

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

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 422
Author(s):  
Francesco De Logu ◽  
Francesca Galli ◽  
Romina Nassini ◽  
Filippo Ugolini ◽  
Sara Simi ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cells ◽  
Cd8 T Cells ◽  
Early Stage ◽  
High Density ◽  
Stage Ii ◽  
Prognostic Impact ◽  
Training Cohort ◽  
Melanoma Patients ◽  
Disease Free

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.

Prolonged Survival of Dendritic Cell–Vaccinated Melanoma Patients Correlates With Tumor-Specific Delayed Type IV Hypersensitivity Response and Reduction of Tumor Growth Factor β-Expressing T Cells

2009 ◽  
Vol 27 (6) ◽  
pp. 945-952 ◽  
Author(s):  
Mercedes N. López ◽  
Cristian Pereda ◽  
Gabriela Segal ◽  
Leonel Muñoz ◽  
Raquel Aguilera ◽  
...  
Keyword(s):  
Immune Response ◽  
Overall Survival ◽  
T Cells ◽  
Growth Factor ◽  
Regulatory T Cells ◽  
Disease Progression ◽  
Stage Iv ◽  
Stage Iii ◽  
Type Iv ◽  
Melanoma Patients

PurposeThe aim of this work was to assess immunologic response, disease progression, and post-treatment survival of melanoma patients vaccinated with autologous dendritic cells (DCs) pulsed with a novel allogeneic cell lysate (TRIMEL) derived from three melanoma cell lines.Patients and MethodsForty-three stage IV and seven stage III patients were vaccinated four times with TRIMEL/DC vaccine. Specific delayed type IV hypersensitivity (DTH) reaction, ex vivo cytokine production, and regulatory T-cell populations were determined. Overall survival and disease progression rates were analyzed using Kaplan-Meier curves and compared with historical records.ResultsThe overall survival for stage IV patients was 15 months. More than 60% of patients showed DTH-positive reaction against the TRIMEL. Stage IV/DTH-positive patients displayed a median survival of 33 months compared with 11 months observed for DTH-negative patients (P = .0014). All stage III treated patients were DTH positive and remained alive and tumor free for a median follow-up period of 48 months (range, 33 to 64 months). DTH-positive patients showed a marked reduction in the proportion of CD4+ transforming growth factor (TGF) β+ regulatory T cells compared to DTH-negative patients (1.54% v 5.78%; P < .0001).ConclusionOur findings strongly suggest that TRIMEL-pulsed DCs provide a standardized and widely applicable source of melanoma antigens, very effective in evoking antimelanoma immune response. To our knowledge, this is the first report describing a correlation between vaccine-induced reduction of CD4+TGFβ+ regulatory T cells and in vivo antimelanoma immune response associated to improved patient survival and disease stability.

scholarly journals Circulating CD8+ MAIT cells correlate with improved outcomes in anti-PD1 treated melanoma patients.

2020 ◽  
Author(s):  
Victoria M Vorwald ◽  
Dana M Davis ◽  
Robert J Van Gulick ◽  
Robert J Torphy ◽  
Jessica S.W. Borgers ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Receptor ◽  
Prospective Clinical Study ◽  
Mait Cells ◽  
Mhc Class I Molecule ◽  
Improved Outcomes ◽  
Melanoma Patients ◽  
Treatment Responses ◽  
Metastatic Sites

While much of the research concerning factors associated with responses to immunotherapies focuses on the contributions of conventional peptide-specific T cells, the role of unconventional T cells, such as mucosal-associated invariant T (MAIT) cells, in human melanoma remains largely unknown. MAIT cells are innate-like T cells expressing a semi-invariant T cell receptor restricted to the non-classical MHC class I molecule MR1 presenting vitamin metabolites derived from bacteria. In this prospective clinical study, we sought to characterize MAIT cells in melanoma patients and determine their association with clinical outcomes. We identified tumor-infiltrating MAIT cells in melanomas across metastatic sites and found that the number of circulating MAIT cells is reduced in melanoma patients. However, circulating MAIT cell frequency is restored by anti-PD1 treatment in responding patients, correlating with treatment responses in which patients with high frequencies of MAIT cells exhibited improved overall survival. These data provide evidence for leveraging MAIT cells and their functions as novel targets for future therapies.

scholarly journals Proportions of blood-borne Vδ1+ and Vδ2+ T-cells are associated with overall survival of melanoma patients treated with ipilimumab

2016 ◽  
Vol 64 ◽  
pp. 116-126 ◽  
Author(s):  
Kilian Wistuba-Hamprecht ◽  
Alexander Martens ◽  
Karin Haehnel ◽  
Marnix Geukes Foppen ◽  
Jianda Yuan ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cells ◽  
Melanoma Patients

Resident and circulating memory T cells persist for years in melanoma patients with durable responses to immunotherapy

immuneACCESS ◽  
2021 ◽  
Author(s):  
J Han ◽  
Y Zhao ◽  
K Shirai ◽  
A Molodtsov ◽  
FW Kolling ◽  
...  
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Melanoma Patients

scholarly journals Checkpoint inhibitor induced hepatitis and the relation with liver metastasis and outcome in advanced melanoma patients

2021 ◽  
Author(s):  
Maaike Biewenga ◽  
Monique K. van der Kooij ◽  
Michel W. J. M. Wouters ◽  
Maureen J. B. Aarts ◽  
Franchette W. P. J. van den Berkmortel ◽  
...  
Keyword(s):  
Overall Survival ◽  
Liver Metastasis ◽  
Combination Therapy ◽  
Real World ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Negative Effect ◽  
Melanoma Patients

Abstract Background Checkpoint inhibitor-induced hepatitis is an immune-related adverse event of programmed cell death protein 1 (PD-1) inhibition, cytotoxic T-lymphocyte associated 4 (CTLA-4) inhibition or the combination of both. Aim of this study was to assess whether checkpoint inhibitor-induced hepatitis is related to liver metastasis and outcome in a real-world nationwide cohort. Methods Data from the prospective nationwide Dutch Melanoma Treatment Registry (DMTR) was used to analyze incidence, risk factors of checkpoint inhibitor-induced grade 3–4 hepatitis and outcome. Results 2561 advanced cutaneous melanoma patients received 3111 treatments with checkpoint inhibitors between May 2012 and January 2019. Severe hepatitis occurred in 30/1620 (1.8%) patients treated with PD-1 inhibitors, in 29/1105 (2.6%) patients treated with ipilimumab and in 80/386 (20.7%) patients treated with combination therapy. Patients with hepatitis had a similar prevalence of liver metastasis compared to patients without hepatitis (32% vs. 27%; p = 0.58 for PD-1 inhibitors; 42% vs. 29%; p = 0.16 for ipilimumab; 38% vs. 43%; p = 0.50 for combination therapy). There was no difference in median progression free and overall survival between patients with and without hepatitis (6.0 months vs. 5.4 months progression-free survival; p = 0.61; 17.0 vs. 16.2 months overall survival; p = 0.44). Conclusion Incidence of hepatitis in a real-world cohort is 1.8% for PD-1 inhibitor, 2.6% for ipilimumab and 20.7% for combination therapy. Checkpoint inhibitor-induced hepatitis had no relation with liver metastasis and had no negative effect on the outcome.

scholarly journals Resident and circulating memory T cells persist for years in melanoma patients with durable responses to immunotherapy

Nature Cancer ◽  
2021 ◽  
Vol 2 (3) ◽  
pp. 300-311
Author(s):  
Jichang Han ◽  
Yanding Zhao ◽  
Keisuke Shirai ◽  
Aleksey Molodtsov ◽  
Fred W. Kolling ◽  
...  
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Melanoma Patients
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