Prognostic Significance of Tumor Infiltrating Lymphocytes in Melanoma

2011 ◽  
Vol 77 (2) ◽  
pp. 188-192 ◽  
Author(s):  
Alison L. Burton ◽  
Brent A. Roach ◽  
Michael P. Mays ◽  
Andrea F. Chen ◽  
Brooke A.R. Ginter ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Cutaneous Melanoma ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Free Survival ◽  
Kaplan Meier ◽  
Major Predictor ◽  
Significant Independent Factor ◽  
Infiltrating Lymphocytes

The prognostic significance of tumor infiltrating lymphocyte (TIL) response in cutaneous melanoma is controversial. This analysis of data from a prospective, randomized trial included patients with cutaneous melanoma ≥ 1.0 mm Breslow thickness who underwent wide local excision and sentinel lymph node (SLN) biopsy. Univariate and multivariate analyses were performed to determine factors associated with TIL response, disease-free survival (DFS), and overall survival (OS). A total of 515 patients were included; TIL response was classified as “brisk” (n = 100; 19.4%) or “non-brisk” (n = 415; 80.6%). Patients in the nonbrisk TIL group were more likely to have tumor-positive SLN (17.6% vs 7%; P = 0.0087). On multivariate analysis, nonbrisk TIL response, increased tumor thickness, and ulceration were significant independent predictors of tumor-positive SLN. By Kaplan-Meier analysis, 5-year DFS rate was 91 per cent for those with a brisk TIL response compared with 86 per cent in the nonbrisk group ( P = 0.41). The 5-year OS rates were 95 per cent versus 84 per cent in the brisk versus nonbrisk TIL groups, respectively ( P = 0.0083). However, on multivariate analysis, TIL response was not a significant independent factor predicting DFS or OS. TIL response is a significant predictor of SLN metastasis but is not a major predictor of DFS or OS.

scholarly journals CCL20/TNF/VEGFA Cytokine Secretory Phenotype of Tumor-Associated Macrophages Is a Negative Prognostic Factor in Cutaneous Melanoma

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3943
Author(s):  
Alba Gutiérrez-Seijo ◽  
Elena García-Martínez ◽  
Celia Barrio-Alonso ◽  
Miriam Pareja-Malagón ◽  
Alejandra Acosta-Ocampo ◽  
...  
Keyword(s):  
Cutaneous Melanoma ◽  
Large Fraction ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Rna Seq ◽  
Primary Cutaneous Melanoma ◽  
Kaplan Meier ◽  
Intracellular Cytokines ◽  
Negative Prognostic Factor

TAMs constitute a large fraction of infiltrating immune cells in melanoma tissues, but their significance for clinical outcomes remains unclear. We explored diverse TAM parameters in clinically relevant primary cutaneous melanoma samples, including density, location, size, and polarization marker expression; in addition, because cytokine production is a hallmark of macrophages function, we measured CCL20, TNF, and VEGFA intracellular cytokines by single-cell multiparametric confocal microscopy. The Kaplan–Meier method was used to analyze correlation with melanoma-specific disease-free survival and overall survival. No significant correlations with clinical parameters were observed for TAM density, morphology, or location. Significantly, higher contents of the intracellular cytokines CCL20, TNF, and VEGFA were quantified in TAMs infiltrating metastasizing compared to non-metastasizing skin primary melanomas (p < 0.001). To mechanistically explore cytokine up-regulation, we performed in vitro studies with melanoma-conditioned macrophages, using RNA-seq to explore involved pathways and specific inhibitors. We show that p53 and NF-κB coregulate CCL20, TNF, and VEGFA in melanoma-conditioned macrophages. These results delineate a clinically relevant pro-oncogenic cytokine profile of TAMs with prognostic significance in primary melanomas and point to the combined therapeutic targeting of NF-kB/p53 pathways to control the deviation of TAMs in melanoma.

Tumor-Infiltrating Lymphocytes Predict Sentinel Lymph Node Positivity in Patients With Cutaneous Melanoma

2007 ◽  
Vol 25 (7) ◽  
pp. 869-875 ◽  
Author(s):  
Rebecca C. Taylor ◽  
Ami Patel ◽  
Katherine S. Panageas ◽  
Klaus J. Busam ◽  
Mary S. Brady
Keyword(s):  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Cutaneous Melanoma ◽  
Prognostic Significance ◽  
Tumor Infiltrating Lymphocytes ◽  
Breslow Thickness ◽  
Anatomic Site ◽  
Primary Cutaneous Melanoma ◽  
Male Sex ◽  
Infiltrating Lymphocytes

Purpose Tumor-infiltrating lymphocytes (TILs) are considered a manifestation of the host immune response to tumor, but the influence of TILs on outcome remains controversial. Studies evaluating the prognostic significance of TILs were published before routine examination of draining lymph nodes by sentinel lymph node (SLN) biopsy, the most important predictor of survival in patients with melanoma. The prognostic implications of TILs were re-evaluated in a large group of patients undergoing SLN biopsy at our institution. Patients and Methods All patients who underwent SLN mapping for primary cutaneous melanoma between January 1996 and July 2005 were evaluated. Univariate and multivariate analyses were performed to assess factors that predict SLN positivity and survival. Factors analyzed included Breslow thickness, ulceration, anatomic site, sex, Clark level, age, mitotic rate, and the presence (brisk or nonbrisk) or absence of TIL. Results Eight hundred eighty-seven patients underwent SLN mapping, and a SLN was identified in 875 patients (98.8%). The SLN was positive for tumor in 156 patients (17.6%). Multivariate analysis revealed that only Breslow thickness (P < .0001), ulceration (P = .0004), male sex (P = .03), and absent TILs (P = .0003) were independently predictive of the presence of SLN metastases. In melanomas with a brisk TIL infiltrate, the probability of a positive SLN was 3.9% as compared with 26.2% for melanomas in which TILs were absent. TILs were not an independent predictive factor for survival. Conclusion The absence of TILs, together with increasing Breslow thickness, presence of ulceration and male sex, predicts SLN metastasis in patients undergoing SLN biopsy for primary cutaneous melanoma.

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 .

scholarly journals Lymphopenia associated with adjuvant chemotherapy after potentially curative surgery for colorectal cancer correlates with recurrence

2016 ◽  
Author(s):  
Masatsune Shibutani ◽  
Kiyoshi Maeda ◽  
Hisashi Nagahara ◽  
Hiroshi Ohtani ◽  
Tetsuro Ikeya ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Multivariate Analysis ◽  
Adjuvant Chemotherapy ◽  
Lymphocyte Count ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Curative Surgery ◽  
Free Survival ◽  
Background Data ◽  
Disease Free

Abstract Objective: The aim of this retrospective study was to evaluate the prognostic significance of lymphopenia associated with chemotherapy in patients with colorectal cancer who received adjuvant chemotherapy after undergoing potentially curative surgery. Summary of background data: Lymphocyte plays an important role in anti-tumor immunity. Lymphopenia is sometimes induced during the period of adjuvant chemotherapy after potentially curative surgery for colorectal cancer. However, the prognostic significance of lymphopenia associated with chemotherapy is unknown. Methods: One hundred and fifteen patients who received adjuvant chemotherapy after potentially curative surgery for stage II/III colorectal cancer were enrolled in this study. All patients were classified into two groups, the lymphopenia group and the normal group, according to minimum lymphocyte count during the period of adjuvant chemotherapy. Lymphopenia was defined as a lymphocyte count of less than 1,000/Ã&#x8e;¼l. Lymphopenia associated with chemotherapy was found in 17 of the 115 patients (14.8%). Results: Lymphopenia was associated with a worse disease-free survival (p=0.018). Moreover, in a multivariate analysis, lymphopenia associated with chemotherapy was identified to be an independent prognostic factor.

Homozygous Deletion of p16, p14 and p15 Is a Poor Prognostic Factor in Adult B-Lineage Acute Lymphoblastic Leukemia, Not in Childhood B-ALL: A Comparison through Deletion and Hypermethylation Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4477-4477
Author(s):  
Miyoung Kim ◽  
Seon-Hee Yim ◽  
Hai Rim Shin ◽  
Nam Sun Cho ◽  
Seong_Ho Kang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Promoter Methylation ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Homozygous Deletion ◽  
P Value ◽  
Free Survival ◽  
Kaplan Meier ◽  
P15 Gene

Abstract Backgrounds: The biologic characteristics of childhood acute lymphoblastic leukemia (ALL) is different from those of adult ALL. Tumor suppressor genes, p16, p14, and p15 gene are inactivated either by promoter methylation, deletion or mutation, however, in leukemia, promoter methylation and deletion are the main mechanisms of inactivation. Aims: To compare the alteration status of p16, p14, and p15 gene in childhood and adult ALL, we analyzed the incidences and the prognostic significances of deletion and hypermethylation of p16, p14, and p15 in childhood and adult B-ALL. The association between alterations of those genes and known cytogenetic prognostic factors (BCR-ABL, TEL-AML, MLL rearrangement, and numerical changes) were also assessed. Methods: A total of 91 newly diagnosed B-ALL patients (61 children, 30 adults) were studied. Interphase fluorescent in situ hybridization study (p16, BCR-ABL, TEL-AML, MLL) and methylation specific PCR were performed using bone marrow mononuclear cells. Numerical changes were assessed by FISH and chromosome analysis. Chi-square test, Fisher’s exact test, Kaplan and Meier method and Cox proportional hazards regression were applied for statistical analysis. Results: The frequencies of homozygous deletion of p16, p14, and p15 were 11.5% in children and 30.0% in adult, showing higher incidence in adults (p=0.029). In overall survival study, homozygous deletion was associated with the worse prognosis in adults (Fig 1, p=0.019), but not in childhood. The incidences of promoter methylation of p16, p14, and p15 were as follows: 34.4%, 14.8%, and 34.4% in children; 26.7%, 10.0%, and 40.0% 26.7% in adults, respectively, with no statistical difference between two groups. No significant association was observed between deletion and hypermethylation. Childhood ALL showed inactivation of p16 (39.3%), p14 (24.6%), and p15 (42.6%), while adult ALL showed inactivation of p16 (46.7%), p14 (33.3%), and p15 (56.7%), with the same order of frequencies, but with higher tendency of methylation in adult ALL. In p14 unmethylated adults, the homozygous deletion had adverse effect on overall survival (OS) (p=0.036). There were no significant association between chromosomal aberrations and promoter methylation in childhood and adult ALL. The children with sole MLL rearrangement showed poorer disease free survival (DFS) than those with sole homozygous deletion with low statistical significance (p=0.059). Homozygous deletion was translated into poor prognosis in OS in adults without MLL rearrangement (p=0.011). Adult with normal karyotype showed shorter OS when accompanied by homozygous deletion, although p value was 0.051. Conclusions: We performed a comprehensive analysis of deletion and hypermethylation of p16, p14, and p15 genes in both childhood and adult B-ALL. Homozygous deletion was more frequent in adults, showing association with shorter OS in adults, but not in children. This difference of distribution and prognostic value between childhood and adult ALL could be one of the explanations for the disparity of clinical outcome. Our results suggest that homozygous deletion is an independent prognostic factor in adult ALL. Table 1. Deletion and methylation profiles of p16, p14, and p15, and their prognostic siginificances P16, P14, and P15 Deletion P16 Methylation P14 Methylation P15 Methylation *P: p value by multivariate analysis †OS: Overall survival ‡DPS: Disease free survival Childhood Frequency 11.5% 34.4% 14.8% 34.4% *P (†OS) 0.853 0.979 0.651 0.591 P (‡DPS) 0.716 0.956 0.809 0.977 Adults Frequency 30.0% 26.7% 10.0% 40.0% P (OS) 0.019 0.151 0 892 0.330 P (DPS) 0.218 0.382 0.079 0.760 Figure 1. Kaplan-Meier curve for childhood and adult B-ALL patients.&#x2028; P value was obtained by multivariate analysis using Cox hazard regression model. (A) Childhood B-ALL (B) B. Adult B-ALL Figure 1. Kaplan-Meier curve for childhood and adult B-ALL patients.&#x2028; P value was obtained by multivariate analysis using Cox hazard regression model. (A) Childhood B-ALL (B) B. Adult B-ALL

scholarly journals Stromal Tumor Infiltrating Lymphocytes (sTILs) as a putative prognostic marker to identify a responsive subset of TNBC in an Indian Breast Cancer Cohort.

2020 ◽  
Author(s):  
Pooja Vaid ◽  
Anirudha Puntambekar ◽  
Rituja Banale ◽  
Ruhi Reddy ◽  
Rohini Unde ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Response To Therapy ◽  
Stromal Tumor ◽  
Breast Cancer Patients ◽  
Infiltrating Lymphocytes ◽  
Disease Free

Objectives Prognostic significance of stromal tumor infiltrating lymphocytes; sTILs is evaluated to identify a responsive subset of TNBC in an Indian cohort of breast cancer patients. Methods A retrospective cohort of breast cancer patients from a single onco-surgeon breast cancer clinic treated with uniform treatment strategy across is evaluated for sTILs. FFPE tissue of primary tumor of invasive breast carcinoma are collected with ethical approvals. Tumor sections blinded for subtypes are stained with H&E and scored for sTILs by a pathologist following Immuno-Oncology TILs working groups scoring guidelines. Results Analysis of 144 primary breast tumors for sTILs scores re-enforces significantly higher infiltration in TNBC tumors than HER2+ve and ER+ve tumors. Higher sTILs scores co-relate with gradually incremental pathological response to therapy specifically in TNBC subset and with better disease-free survival outcomes. Within TNBC, older and post-menopausal patients harbor higher scores of sTILs. Conclusion Despite a small cohort of breast cancer patients, TNBC subtype reflected significantly higher scores of sTILs with better response to therapy and disease-free outcomes as compared to other breast cancer subtypes. A larger number of breast cancer patients from an Indian cohort will strengthen the findings to establish sTILs as a marker to identify a responsive subset of TNBC.

Association of mucin production and survival in colon cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 512-512 ◽  
Author(s):  
John Hogan ◽  
Georges Samaha ◽  
John Burke ◽  
David Waldron ◽  
Eoin Condon ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Free Survival ◽  
Mucin Production ◽  
Kaplan Meier ◽  
The Relationship ◽  
Disease Free

512 Background: Debate persists regarding the relationship between mucin production and cancer-related outcome following curative resection for colon cancer. Lack of consensus is due to (amongst other factors) discrepancies in definition, small cohort studies and the integration of both colon and rectal cancers. This study characterizes the relationship between mucin production and cancer-related outcome in an homogenous single-institute based cohort. Methods: A database spanning demographics, clinico-pathologic characteristics and prognostic factors was generated for all patients undergoing curative-intent colonic resection in the interval 2000 to 2010. Patients were categorized simply as mucin producing (i.e. MC) or non-mucin producing adenocarcinoma (NMC). Primary outcomes included overall survival (time to death from any cause) and disease free survival (time to loco-regional and systemic recurrence). Trends were established for MC and NMC using Kaplan-Meier estimates, plotted and compared using log-rank analysis. Findings significant on univariate analysis were incorporated into multivariate analysis. Cox proportional hazards model was employed to determine the associated hazard of both death and disease recurrence in each group. Statistical analysis was performed using R version 2.15. P < 0.05 was considered significant. Results: 77 mucinous carcinomas (MC) and 358 non mucinous carcinomas (NMC) were included. On univariate analysis, MC was associated with improved overall survival (OS) (P=0.007). Both N1 (HR 1.625, P=0.011) and N2 (HR 2.7, P<0.001) status were associated with adverse OS. On multivariate analysis, MC approached but did not reach statistical significance for improved OS (HR 0.543, P=0.061). A comparison of Kaplan-Meier estimates for overall survival in MC and NMC groups indicated that OS was significantly improved in the MC cohort (P=0.011). There was no difference in disease free survival (P=0.224). Systemic recurrence was greater in the NMC group (P=0.042). Conclusions: Mucin production in colonic adenocarcinoma appears associated with improved overall but not disease-free survival. In addition, the absence of mucin was associated with adverse systemic but not local recurrence.

Association of intratumoral PD-L1 expression with survival of patients with Epstein-Barr virus-associated gastric cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15590-e15590
Author(s):  
Jong Gwang Kim ◽  
Byung Woog Kang ◽  
Yee Soo Chae ◽  
Soo Jung Lee ◽  
In Hee Lee ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Multivariate Analysis ◽  
Epstein Barr Virus ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Barr Virus ◽  
Significant Difference ◽  
Epstein Barr

e15590 Background: The present study analyzed the expression of tumoral (t-) PD-L1/L2 and stromal (str-) PD-L1/L2, and their impacts on the survival of a relatively large group of Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC). Methods: After reviewing 1318 consecutive cases of surgically resected or endoscopic submucosal dissected gastric cancers, 120 patients were identified as EBV-positive using EBV-encoded RNA in situ hybridization. Immunohistochemistry of PD-L1 and PD-L2 was carried out and the intensity was scored as an intensity score 0 (no staining), 1 (weak intensity), 2 (intermediate intensity), and 3 (high intensity). The expression was also evaluated in tumor tissues and stromal immune cells and divided into two groups (2 and 3 were interpreted as a positive result). Results: Among the 120 patients, 57 patients (47.5%) and 66 patients (55.0%) were determined as t-PD-L1-positive and str-PD-L1 positive, while 23 patients (19.2%) and 41 patients (34.2%) were determined as t-PD-L2-positive and str-PD-L2 positive. In a univariate analysis, t-PD-L1-positive was significantly associated shorter disease-free survival (DFS, P = 0.032), yet not overall survival (P = 0.482). In a multivariate analysis using a Cox proportional hazard model adjusted for age, pTNM stage, gender, WHO classification, and tumor-infiltrating lymphocytes, t-PD-L1 positivity was independently associated with poor DFS (Hazard ratio = 4.183, P = 0.044). Meanwhile, in the univariate analysis, t-PD-L2-positive and str-PD-L2-positive showed a better DFS trend than t-PD-L2-negative and str-PD-L2-negative, respectively (P = 0.071 and P = 0.092). However, t-PD-L2 and str-PD-L2 expressions showed no prognostic significance on DFS in the multivariate analysis. Conclusions: The level of t-PD-L1 expression represents a significant difference for DFS in patients with EBVaGC. The current findings support the concept that PD-L1 may be a prognostic parameter for predicting patient outcome and act as a therapeutic target in EBVaGC.

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