Infusion of Melan-A/Mart-1 specific tumor-infiltrating lymphocytes enhanced relapse-free survival of melanoma patients

2006 ◽  
Vol 56 (4) ◽  
pp. 515-526 ◽  
Author(s):  
Houssem Benlalam ◽  
Virginie Vignard ◽  
Amir Khammari ◽  
Annabelle Bonnin ◽  
Yann Godet ◽  
...  
Keyword(s):  
Tumor Infiltrating Lymphocytes ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Specific Tumor ◽  
Melanoma Patients ◽  
Infiltrating Lymphocytes

Prognostic impact of tumor-infiltrating lymphocytes in non-small cell lung carcinomas

2021 ◽  
pp. 021849232110421
Author(s):  
Mona Mlika ◽  
Ayoub Saidi ◽  
Nesrine Mejri ◽  
Mehdi Abdennadher ◽  
Chokri Haddouchi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Small Cell ◽  
Prognostic Impact ◽  
Small Cell Lung ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Lung Carcinomas ◽  
Forkhead Box ◽  
Infiltrating Lymphocytes

Introduction Tumor-infiltrating lymphocytes represent a pivotal component of the host anti-tumor response. Thus, they considerably influence the evolution of cancers including non-small cell lung carcinomas. Even if, this important role is consensual, many discordant results are published in the literature about the prognostic role of the different populations of tumor-infiltrating lymphocytes. The aim of our work was to evaluate the prognostic impact of CD8+, CD4+, and forkhead box protein P3+ lymphocytes in the tumor microenvironment of non-small cell lung carcinomas. Methods We conducted a retrospective descriptive study, which included non-small cell lung carcinomas diagnosed in the department of pathology and followed in the medical oncology department of the same hospital between 2011 and 2015. Tumor-infiltrating lymphocytes were analyzed by the immunohistochemical method for forkhead box protein P3, CD4, and CD8. Intratumoral and stromal-labeled lymphocytes were quantified by manual counting at high magnification (×400). Forkhead box protein P3+/CD8+, forkhead box protein P3+/CD4+, and CD8+/CD4+ ratios were subsequently calculated. The prognostic value of tumor-infiltrating lymphocytes was assessed in respect of overall survival, recurrence-free survival, and relapse-free survival. Results Thirty-nine patients were included. The mean age of patients was 59.6 years. A complete surgical resection ( p = 0.009), and a CD8/CD4 ratio ( p = 0.008) were prognostic factors for overall survival. Complete surgical resection ( p = 0.003), the forkhead box protein P3/CD8 ( p = 0.005), and forkhead box protein P3/CD4 ( p = 0.037) ratios were prognostic factors for recurrence-free survival. The CD8+ tumor-infiltrating lymphocytes rate ( p = 0.037) was a prognostic factor for relapse-free survival with a threshold of 67.8/high power field. Microscopic subtype ( p = 0.037) was a prognostic factor for relapse-free survival when only adenocarcinoma and squamous cell carcinoma were considered. In multivariate analysis, age ( p = 0.004) and a CD8/CD4 ratio ( p = 0.016) were independent predictors of overall survival. Conclusion Despite the limitations of our study, our results confirm the prognostic value of tumor-infiltrating lymphocytes in non-small cell lung carcinomas and the importance of the combined quantification of their different subpopulations.

scholarly journals Tumor microenvironment in triple-negative breast cancer: the correlation of tumor-associated macrophages and tumor-infiltrating lymphocytes

2021 ◽  
Author(s):  
H. Kuroda ◽  
T. Jamiyan ◽  
R. Yamaguchi ◽  
A. Kakumoto ◽  
A. Abe ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cytotoxic T Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Tumor Associated Macrophages ◽  
Free Survival ◽  
Infiltrating Lymphocytes

Abstract Purpose Immune cells such as cytotoxic T cells, helper T cells, B cells or tumor-associated macrophages (TAMs) contribute to the anti-tumor response or pro-tumorigenic effect in triple negative breast cancer (TNBC). The interrelation of TAMs, T and B tumor-infiltrating lymphocytes (TILs) in TNBC has not been fully elucidated. Methods We evaluated the association of tumor-associated macrophages, T and B TILs in TNBC. Results TNBCs with a high CD68+, CD163+ TAMs and low CD4+, CD8+, CD20+ TILs had a significantly shorter relapse-free survival (RFS) and overall survival (OS) than those with low CD68+, CD163+ TAMs and high CD4+, CD8+, CD20+ TILs. TNBCs with high CD68+ TAMs/low CD8+ TILs showed a significantly shorter RFS and OS and a significantly poorer prognosis than those with high CD68+ TAMs/high CD8+ TILs, low CD68+ TAMs/high CD8+ TILs, and low CD68+/low CD8+. TNBCs with high CD163+ TAMs/low CD8+, low CD20 + TILs showed a significantly shorter RFS and OS and a significantly poorer prognosis than those with high CD163+ TAMs/high CD8+ TILs and high CD163+ TAMs /high CD20+ TILs. Conclusions Our study suggests that TAMs further create an optimal tumor microenvironment (TME) for growth and invasion of cancer cells when evasion of immunoreactions due to T and B TILs occurs. In TNBCs, all these events combine to affect prognosis. The process of TME is highly complex in TNBCs and for an improved understanding, larger validation studies are necessary to confirm these findings.

scholarly journals Can the plasma PD-1 levels predict the presence and efficiency of tumor-infiltrating lymphocytes in patients with metastatic melanoma?

2019 ◽  
Vol 11 ◽  
pp. 175883591984887 ◽  
Author(s):  
Lorena Incorvaia ◽  
Giuseppe Badalamenti ◽  
Gaetana Rinaldi ◽  
Juan Lucio Iovanna ◽  
Daniel Olive ◽  
...  
Keyword(s):  
Immune Response ◽  
Overall Survival ◽  
Survival Rate ◽  
Metastatic Melanoma ◽  
Braf Mutation ◽  
Primary Melanoma ◽  
Tumor Infiltrating Lymphocytes ◽  
Enzyme Linked Immunosorbent Assay ◽  
Melanoma Patients ◽  
Infiltrating Lymphocytes

Background: The immune response in melanoma patients is locally affected by presence of tumor-infiltrating lymphocytes (TILs), generally divided into brisk, nonbrisk, and absent. Several studies have shown that a greater presence of TILs, especially brisk, in primary melanoma is associated with a better prognosis and higher survival rate. Patients and Methods: We investigated by enzyme-linked immunosorbent assay (ELISA) the correlation between PD-1 levels in plasma and the presence/absence of TILs in 28 patients with metastatic melanoma. Results: Low plasma PD-1 levels were correlated with brisk TILs in primary melanoma, whereas intermediate values correlated with the nonbrisk TILs, and high PD-1 levels with absent TILs. Although the low number of samples did not allow us to obtain a statistically significant correlation between the plasma PD-1 levels and the patients’ overall survival depending on the absence/presence of TILs, the median survival of patients having brisk type TILs was 5 months higher than that of patients with absent and nonbrisk TILs. Conclusions: This work highlights the ability of measuring the plasma PD-1 levels in order to predict the prognosis of patients with untreated metastatic melanoma without a BRAF mutation at the time of diagnosis.

scholarly journals An open source automated tumor infiltrating lymphocyte algorithm for prognosis in melanoma

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Balazs Acs ◽  
Fahad Shabbir Ahmed ◽  
Swati Gupta ◽  
Pok Fai Wong ◽  
Robyn D. Gartrell ◽  
...  
Keyword(s):  
Open Source ◽  
Open Source Software ◽  
Tumor Infiltrating Lymphocytes ◽  
Independent Prognostic Marker ◽  
Scoring Algorithm ◽  
Multivariable Analyses ◽  
Melanoma Patients ◽  
Independent Association ◽  
Infiltrating Lymphocytes ◽  
Hematoxylin Eosin

AbstractAssessment of tumor infiltrating lymphocytes (TILs) as a prognostic variable in melanoma has not seen broad adoption due to lack of standardization. Automation could represent a solution. Here, using open source software, we build an algorithm for image-based automated assessment of TILs on hematoxylin-eosin stained sections in melanoma. Using a retrospective collection of 641 melanoma patients comprising four independent cohorts; one training set (N = 227) and three validation cohorts (N = 137, N = 201, N = 76) from 2 institutions, we show that the automated TIL scoring algorithm separates patients into favorable and poor prognosis cohorts, where higher TILs scores were associated with favorable prognosis. In multivariable analyses, automated TIL scores show an independent association with disease-specific overall survival. Therefore, the open source, automated TIL scoring is an independent prognostic marker in melanoma. With further study, we believe that this algorithm could be useful to define a subset of patients that could potentially be spared immunotherapy.

scholarly journals Tumor-Infiltrating Lymphocytes and Prognosis: A Pooled Individual Patient Analysis of Early-Stage Triple-Negative Breast Cancers

2019 ◽  
Vol 37 (7) ◽  
pp. 559-569 ◽  
Author(s):  
Sherene Loi ◽  
Damien Drubay ◽  
Sylvia Adams ◽  
Giancarlo Pruneri ◽  
Prudence A. Francis ◽  
...  
Keyword(s):  
Triple Negative ◽  
Early Stage ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Cox Proportional Hazards ◽  
Prognostic Information ◽  
Free Survival ◽  
Node Negative ◽  
Infiltrating Lymphocytes ◽  
Disease Free

Purpose The aim of the current study was to conduct a pooled analysis of studies that have investigated the prognostic value of tumor-infiltrating lymphocytes (TILs) in early-stage triple negative breast cancer (TNBC). Methods Participating studies had evaluated the percentage infiltration of stromally located TILs (sTILs) that were quantified in the same manner in patient diagnostic samples of early-stage TNBC treated with anthracycline-based chemotherapy with or without taxanes. Cox proportional hazards regression models stratified by trial were used for invasive disease-free survival (iDFS; primary end point), distant disease-free survival (D-DFS), and overall survival (OS), fitting sTILs as a continuous variable adjusted for clinicopathologic factors. Results We collected individual data from 2,148 patients from nine studies. Average age was 50 years (range, 22 to 85 years), and 33% of patients were node negative. The average value of sTILs was 23% (standard deviation, 20%), and 77% of patients had 1% or more sTILs. sTILs were significantly lower with older age ( P = .001), larger tumor size ( P = .01), more nodal involvement ( P = .02), and lower histologic grade ( P = .001). A total of 736 iDFS and 548 D-DFS events and 533 deaths were observed. In the multivariable model, sTILs added significant independent prognostic information for all end points (likelihood ratio χ2, 48.9 iDFS; P < .001; χ2, 55.8 D-DFS; P < .001; χ2, 48.5 OS; P < .001). Each 10% increment in sTILs corresponded to an iDFS hazard ratio of 0.87 (95% CI, 0.83 to 0.91) for iDFS, 0.83 (95% CI, 0.79 to 0.88) for D-DFS, and 0.84 (95% CI, 0.79 to 0.89) for OS. In node-negative patients with sTILs ≥ 30%, 3-year iDFS was 92% (95% CI, 89% to 98%), D-DFS was 97% (95% CI, 95% to 99%), and OS was 99% (95% CI, 97% to 100%). Conclusion This pooled data analysis confirms the strong prognostic role of sTILs in early-stage TNBC and excellent survival of patients with high sTILs after adjuvant chemotherapy and supports the integration of sTILs in a clinicopathologic prognostic model for patients with TNBC. This model can be found at www.tilsinbreastcancer.org .

PD-L1 specific tumor infiltrating lymphocytes occur frequently in melanoma and HNSCC patients.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 11083-11083
Author(s):  
Niels Junker ◽  
Marco Donia ◽  
Rikke Andersen ◽  
Mads Hald Andersen ◽  
Inge Marie Svane
Keyword(s):  
Tumor Infiltrating Lymphocytes ◽  
Specific Tumor ◽  
Infiltrating Lymphocytes
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