scholarly journals The prevalence and prognostic impact of tumor-infiltrating lymphocytes in uterine carcinosarcoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jesse Lopes da Silva ◽  
Lucas Zanetti de Albuquerque ◽  
Fabiana Resende Rodrigues ◽  
Guilherme Gomes de Mesquita ◽  
Cláudia Bessa Pereira Chaves ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Tissue Microarrays ◽  
Prognostic Impact ◽  
Uterine Carcinosarcoma ◽  
Free Survival ◽  
Checkpoint Signaling ◽  
Advanced Stages ◽  
Infiltrating Lymphocytes

Abstract Objective To examine the prevalence and prognostic role of tumor microenvironment (TME) markers in uterine carcinosarcoma (UCS) through immunohistochemical characterization. Methods The internal database of our institution was queried out for women with UCS who underwent surgery and thereafter postoperative chemotherapy with carboplatin and paclitaxel between January 2012 and December 2017. Tissue microarrays containing surgical samples of UCS from 57 women were assessed by immunohistochemistry for CD3, CD4, CD8, FOXP3, PD-1, PD-L1, and PD-L2. Results The mean age was 65.3 years (range, 49 to 79 years). For the epithelial component (E), CD3_E and CD4_E were highly expressed in 38 (66.7%) and in 40 (70.1%) patients, respectively, and were significantly associated with more advanced stages (p = 0.038 and p = 0.025, respectively). CD8_E was highly expressed in 42 (73.7%) patients, FOXP3_E 16 (28.1%), PD-1_E 35 (61.4%), PD-L1_E 27 (47.4%) and PD-L2_E 39 (68.4%). For the sarcomatous component (S), the prevalence of high expression was: CD3_S 6 (10.5%), CD4_S 20 (35.1%), CD8_S 44 (77.2%), FOXP3_S 8 (14%), PD-1_S 14 (24.6%), PD-L1_S 14 (24.6%) and PD-L2_S 8 (14%). By multivariate analysis, the CD8/FOXP3_S ratio (p = 0.026), CD4_E (p = 0.010), PD-L1_E (p = 0.013) and PD-L1_S (p = 0.008) markers significantly influenced progression-free survival. CD4/FOXP3_S ratio (p = 0.043), PD-1_E (p = 0.011), PD-L1_E (p = 0.036) and PD-L1_S (p = 0.028) had a significant association with overall survival. Conclusion Some differences in UCS clinical outcomes may be due to the subtype of TILs and PD-1/PD-L1 axis immune checkpoint signaling.

scholarly journals Prognostic Impact of Tumor-Infiltrating Lymphocytes and Neutrophils on Survival of Patients with Upfront Resection of Pancreatic Cancer

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 39 ◽  
Author(s):  
Rainer C. Miksch ◽  
Markus B. Schoenberg ◽  
Maximilian Weniger ◽  
Florian Bösch ◽  
Steffen Ormanns ◽  
...  
Keyword(s):  
Hot Spots ◽  
Immune Cell ◽  
Progression Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Ductal Adenocarcinoma ◽  
Prognostic Impact ◽  
Free Survival ◽  
Staging Systems ◽  
Infiltrating Lymphocytes ◽  
The Impact

In patients with pancreatic ductal adenocarcinoma (PDAC), the tumor microenvironment consists of cellular and stromal components that influence prognosis. Hence, tumor-infiltrating lymphocytes (TILs) may predict prognosis more precisely than conventional staging systems. Studies on the impact of TILs are heterogeneous and further research is needed. Therefore, this study aims to point out the importance of peritumoral TILs, tumor-infiltrating neutrophils (TINs), and immune subtype classification in PDAC. Material from 57 patients was analyzed with immunohistochemistry performed for CD3, CD8, CD20, CD66b, α-sma, and collagen. Hot spots with peritumoral TILs and TINs were quantified according to the QTiS algorithm and the distance of TILs hot spots to the tumor front was measured. Results were correlated with overall (OS) and progression-free survival (PFS). High densities of peritumoral hot spots with CD3+, CD8+, and CD20+ TILs correlated significantly with improved OS and PFS. Combined immune cell subtypes predicted improved OS and PFS. High infiltration of CD3+ TILs predicted progression after 12 months. The location of TILs’ hot spots and their distance to the tumor front did not correlate with patient survival. Peritumoral TILs and the composition of the stroma predict OS and PFS in PDAC.

scholarly journals Spatial analysis of tumor infiltrating lymphocytes based on deep learning using histopathology image to predict progression-free survival in colorectal cancer

2021 ◽  
Author(s):  
Hongming Xu ◽  
Yoon Jin Cha ◽  
Jean R. Clemenceau ◽  
Jinhwan Choi ◽  
Sung Hak Lee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Multivariate Analysis ◽  
Interobserver Agreement ◽  
Progression Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Kappa Coefficient ◽  
Prognostic Impact ◽  
Free Survival ◽  
Invasive Margin ◽  
Infiltrating Lymphocytes

AbstractPurposeThis study aimed to explore the prognostic impact of spatial distribution of tumor infiltrating lymphocytes (TILs) quantified by deep learning (DL) approaches based on digitalized whole slide images stained with hematoxylin and eosin in patients with colorectal cancer (CRC).MethodsThe prognostic impact of spatial distributions of TILs in patients with CRC was explored in the Yonsei cohort (n=180) and validated in the TCGA cohort (n=268). Concurrently, two experienced pathologists manually measured TILs at the most invasive margin as 0-3 by the Klintrup-Mäkinen (KM) grading method and compared to DL approaches. Interobserver agreement for TILs was measured using Cohen’s kappa coefficient.ResultsOn multivariate analysis of spatial TILs features derived by DL approaches and clinicopathological variables including tumor stage, Microsatellite instability, and KRAS mutations, TILs densities within 200 μm of the invasive margin (f_im200) was remained as the most significant prognostic factor for progression-free survival (PFS) (HR 0.004 [95% CI, 0.0001-0.1502], p=.002) in the Yonsei cohort. On multivariate analysis using the TCGA dataset, f_im200 retained prognostic significance for PFS (HR 0.031, [95% CI 0.001-0.645], p=.024). Interobserver agreement of manual KM grading based on Cohen’s kappa coefficient was insignificant in the Yonsei (κ=.109) and the TCGA (κ=.121), respectively. The survival analysis based on KM grading showed statistically significant different PFS from the TCGA cohort, but not the Yonsei cohort.ConclusionsAutomatic quantification of TILs at the invasive margin based on DL approaches showed a prognostic utility to predict PFS, and could provide robust and reproducible TILs density measurement in patients with CRC.Data and Code AvailabilitySource code and data used for this study is available at the following link: https://github.com/hwanglab/TILs_Analysis

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.

The role of complete response in multiple myeloma

Blood ◽  
2009 ◽  
Vol 114 (15) ◽  
pp. 3139-3146 ◽  
Author(s):  
Jean-Luc Harousseau ◽  
Michel Attal ◽  
Herve Avet-Loiseau
Keyword(s):  
Multiple Myeloma ◽  
Progression Free Survival ◽  
Complete Response ◽  
High Dose ◽  
Prognostic Impact ◽  
Free Survival ◽  
Depth Of Response ◽  
The Impact ◽  
Good Partial Response

AbstractIn multiple myeloma (MM), the impact of complete response (CR) could be shown only after introduction of high-dose therapy plus autologous stem cell transplantation (ASCT). In the context of ASCT, achieving CR (negative immunofixation and normal bone marrow) or at least very good partial response is associated with longer progression-free survival and in most studies longer survival. With novel agents, high CR rates are achieved and this prognostic impact of CR is being shown as well, both in relapsed and in newly diagnosed MM. However the benefit of CR achievement depends on the type of treatment and is not identical for all patients. In elderly patients, treatments inducing more CR may be more toxic. Although CR achievement is necessary in patients with poor-risk disease, it might not be as critical for long survival in more indolent MM. CR achievement is not the only objective of treatment because it is possible to further improve the depth of response and the outcome by continuing treatment after CR achievement. Finally, there are several levels of CR and in the future it will be necessary to confirm the prognostic impact of immunophenotypic or molecular CR or of CR defined by imaging procedures.

scholarly journals Intratumoral immune cells expressing PD-1/PD-L1 and their prognostic implications in cancer: a meta-analysis

2018 ◽  
Vol 33 (4) ◽  
pp. 467-474 ◽  
Author(s):  
Younghoon Kim ◽  
Xianyu Wen ◽  
Nam Yun Cho ◽  
Gyeong Hoon Kang
Keyword(s):  
Overall Survival ◽  
Immune Cells ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Free Survival ◽  
Tissue Sections ◽  
Infiltrating Lymphocytes ◽  
Disease Free

Background: The prognostic value of immune cells expressing programmed cell death 1 (PD-1) and PD-1 ligand 1 (PD-L1) in cancer are controversial, and the potential differential impact of using tissue microarrays and whole tissue sections to assess the positivity of immune cells has not been addressed. Methods: The current study included 30 eligible studies with 7251 patients that evaluated the relationship between tumor-infiltrating lymphocytes expressing PD-1/PD-L1 and overall survival and disease-free survival, or progression-free survival. Subgroup analysis was based on the tissue type of cancer and the type of tissue sampling (tissue microarray or whole tissue section). Results: In the meta-analysis, PD-1-positive and PD-L1-positive tumor-infiltrating lymphocytes had a positive effect on disease-free survival or progression-free survival (hazard ratio [HR] 0.732; 95% confidence interval [CI] 0.565, 0.947; and HR 0.727; 95% CI 0.584, 0.905, respectively). PD-L1-positive tumor-infiltrating lymphocytes had a positive impact on overall survival in studies using tissue microarray (HR 0.586; 95% CI 0.476, 0.721), but had a poor impact when only whole tissue sections were considered (HR 1.558; 95% CI 1.232, 1.969). Lung cancer was associated with good overall survival and disease-free survival (HR 0.639; 95% CI 0.491, 0.831; and HR 0.693; 95% CI 0.538, 0.891, respectively) for PD-1-positive tumor-infiltrating lymphocytes, and colorectal cancer showed favorable disease-free survival (HR 0.471; 95% CI 0.308, 0.722) for PD-L1-positive tumor-infiltrating lymphocytes. Conclusion: Immune cells expressing PD-1 and PD-L1 within tumors are associated with the prognosis. However, the correlation may vary among different tumor types and by the type of tissue sampling used for the assessment.

scholarly journals The tumor-infiltrating effector regulatory T cell:CD8+ lymphocyte ratio in invasive breast cancer

2019 ◽  
Author(s):  
Morihito Okada ◽  
Noriko Goda ◽  
Shinsuke Sasada ◽  
Hideo Shigematsu ◽  
Norio Masumoto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Invasive Breast Cancer ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Compete Response ◽  
Infiltrating Lymphocytes

Abstract Background Tumor-infiltrating lymphocytes (TILs) in breast cancer comprise immunostimulating and immunosuppressive components. Although FOXP3+ TILs are prototypical immunosuppressive TILs, only effector regulatory T cells (eTreg), a subset of immunosuppressive FOXP3+ TILs, are undetectable on immunohistochemical staining. This study aimed to evaluate the immunosuppressive potential of eTregs and the role of prototypical immunostimulatory CD8+ TILs in invasive breast cancer. Methods Fresh TILs extracted from 84 invasive breast cancer patients were analyzed via flow cytometry. We evaluated eTregs (CD4+FOXP3highCD45RA−), other FOXP3+ Treg subsets (naïve and non-Tregs), and total CD8+CD4- TILs. Clinicopathological factors, including histopathological characteristics, were also assessed. Results The median eTreg proportion of the total CD4+TILs was 18.7% (interquartile range [IQR], 16.4–25.5%); CD8+TILs, 124% (IQR, 87.5–140%). The proportion of eTregs to total FOXP3+ TILs varied (median, 65.6%; range, 10.1–93.2%). In an immunosuppression assay, only eTregs displayed potent immunosuppression; however, other Treg subsets did not. Among 39 patients who received neoadjuvant chemotherapy, eTreg subsets and pathological compete response (pCR) did not differ significantly, while pCR rates were significantly higher among individuals with a high than those with a low CD8+/eTreg ratio (90.2% vs 33.3%; P<0.05). Among all patients, a high CD8+/eTreg ratio tended to be associated with better disease-free survival rather than a low CD8+/eTreg ratio (P=0.09). Conclusions The CD8+/eTreg ratio is simple, optimal indicator of cancer immunity, and a high CD8+/eTreg ratio enhances the prognosis and treatment response in invasive breast cancer patients. However, further studies are required to validate the present findings.

scholarly journals Prognostic value of tumor-infiltrating lymphocytes in gliomas: A Systematic Review

2020 ◽  
Author(s):  
yanlin song ◽  
Jing Zhang ◽  
Yu Liu ◽  
Xuelei Ma
Keyword(s):  
Poor Prognosis ◽  
Progression Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
High Density ◽  
Cochrane Library ◽  
Potential Candidate ◽  
Prognostic Role ◽  
China National Knowledge Infrastructure ◽  
Infiltrating Lymphocytes

Abstract Background: Glioma is the most common primary brain tumor with poor prognosis. Some studies have learned the prognostic role of tumor infiltrating lymphocytes (TILs) in gliomas. But conflict conclusions were drawn by these studies. In order to reach an agreement, we systematically performed a meta-analysis.Method: A systematic literature research was conducted on the Web of Science, EMBASE, PubMed, Cochrane Library and China National Knowledge Infrastructure. The eligible articles which met the inclusion criteria were included in our study. The clinical outcomes of included patients were defined as progression-free survival (PFS) and overall survival (OS). The basic characteristics and relevant data were extracted. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled to evaluate the prognostic role of TILs in gliomas. Newcastle Ottawa Scale (NOS) was used to assess the quality of included studies.Results: Eight articles published from 2008 to 2019 were finally included in our study. And 25 studies were conducted in these articles. We assessed the prognostic role of TILs in gliomas by subgroup analysis according to the subtypes of TILs. The pooled HRs for OS revealed that high density of CD3+ and CD4+ TILs were related to the poor prognosis of gliomas (HR for CD3+ TILs=1.266; HR for CD4+ TILs= 2.128). The pooled HR for PFS indicated that only high density of FOXP3+ TILs were related to poor prognosis (HR=2.785; 95%CI=1.848, 4.197).Conclusion: High density of CD3+ and CD4+ TILs may be a potential candidate for predicting poor OS of gliomas while high density of FOXP3+ TILs may serve as a good biomarker for predicting poor PFS of gliomas.

Prognostic impact of tumor-infiltrating lymphocytes (TIL's) and stromal-infiltrating lymphocytes (SIL's) in triple-negative breast cancer.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 83-83
Author(s):  
Santiago Sherwell-Cabello ◽  
Antonio Maffuz-Aziz ◽  
Diego A Camacho-Ramírez ◽  
Verónica Bautista-Piña ◽  
Nina P Ríos-Luna ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Statistical Significance ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Prognostic Impact ◽  
Advanced Stages ◽  
Infiltrating Lymphocytes

83 Background: Immune response seems to improve outcome in women with Triple-Negative Breast Cancer (TNBC). Recent data suggests that the presence of Tumor-Infiltrating Lymphocytes is an independent factor associated with better prognosis. In this study, we evaluate the prognostic impact of both TIL´s and SIL´s in patients with TNBC. Methods: Data on women diagnosed with TNBC between 2005 and 2013, was collected by retrospectively reviewing at our institute. The rate of intratumoral and/or stromal lymphocytes was evaluated in all hematoxylin and eosin-stained histopathologic sections according to Denkert et al. The five-year disease-free survival (DFS) and overall survival (OS) were compared between groups with the presence or absence of TIL´s or SIL´s. Demographic and clinical characteristics were assessed, variables with a statistical significance between groups were analyzed in a multivariate analysis. Results: A total of 172 patients with TNBC treated at this institution were included with a mean age of 49.8 years. A complete absence of tumor lymphocytes was found in 88 patients while the presence of intratumoral, stromal or both was found in 84 (48.8%). A mean follow-up of 46.12 months showed significantly higher rates of both DFS and OS in women with SIL´s and TIL´s (p = 0.014 and 0.042 respectively) in locally advanced stages (LAS), regardless the rate of infiltrating lymphocytes found [Table 1]. SIL´s are correlated with a better prognosis compared with TIL´s (p = 0.028 and 0.091 respectively). Non-significant differences were found in early stages (p= 0.255). Conclusions: These results show that the presence of SIL´s or TIL´s are strongly associated with higher rates of DFS and OS in LAS, especially when SIL´s are found, suggesting that immunity seems to play a key role regarding the outcome in women with TNBC. Independent of the rate of lymphocytic infiltrate, its presence has a statistical significance. Because it is a feasible and inexpensive test that can be used as a prognostic predictor, we suggest assessing both SIL's and TIL's in histopathologic biopsies of patients with TNBC. [Table: see text]

Viagenpumatucel-L (HS-110) plus nivolumab in patients with advanced non-small cell lung cancer (NSCLC).

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 101-101
Author(s):  
Daniel Morgensztern ◽  
Lyudmila Bazhenova ◽  
Saiama Naheed Waqar ◽  
Lori McDermott ◽  
Jeff Hutchins ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Objective Response ◽  
Progression Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Tumor Stroma ◽  
Free Survival ◽  
Grade 5 ◽  
Previously Treated ◽  
Infiltrating Lymphocytes

101 Background: Viagenpumatucel-L (HS-110) is an allogeneic cellular vaccine derived from a human lung adenocarcinoma (AD) cell line transfected with the gp96-Ig fusion protein. DURGA is a multi-cohort study evaluating the combination of HS-110 and immune checkpoint blockers (ICBs) in patients with advanced NSCLC. Here we report the initial two cohorts with the combination of HS-110 and nivolumab. Methods: Patients (pts) with previously treated NSCLC received 1 X 107 HS-110 cells weekly for the first 18 weeks and nivolumab 3 mg/kg or 240 mg every 2 weeks until intolerable toxicity or tumor progression. Tissue was tested at baseline for PD-L1 expression (≥ 1% or < 1%) and tumor infiltrating lymphocytes (TILs). TIL high was defined by more than 10% CD8+ lymphocytes in the tumor stroma. Pts in cohort A had never received, and pts in cohort B had received, prior ICBs. The primary objectives were safety and objective response rates (ORR). Results: As of the August 2018 data cut-off, there were 43 pts enrolled into cohort A (40 AD and 3 squamous cell carcinoma [SCC]) and 18 pts in cohort B (15 AD and 3 SCC). In cohort A, 14 pts (32.6%) were TIL high, 13 (30.2%) TIL low and 16 (37.2%) TIL unknown. ORR, disease control rate (DCR), median progression-free survival (PFS) and 1 year PFS were 18.6%, 48.8%, 1.9 months and 23.9% respectively in cohort A, with median follow up of 432 days. ORR, DCR, and PFS were 22%, 50% and 2.2 months respectively in cohort B, with median follow up of 43 days. The median overall survival (mOS) was not reached in either cohort. In cohort A, TIL low at baseline was associated with increased mOS compared to TIL high (not reached vs 13.8 months, hazard ratio [HR] 0.23, 95% CI 0.068-0.81, p = 0.04). There were no differences in mOS according to PD-L1 status in cohort A (p = 0.82). 57 (93%) pts experienced at least one adverse event (AE), of which 39 (64%) were grade 1 or 2. The most common AEs were fatigue (31%), cough and diarrhea (19.7% each). There were 2 grade 5 AEs (3.3%) caused by pulmonary embolism and tumor progression, neither considered to be treatment related. Conclusions: The combination of HS-110 and nivolumab is safe with encouraging preliminary efficacy data. The study is ongoing and additional populations are being explored. Clinical trial information: NCT02439450.

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