Increased CD3+, CD8+, or FoxP3+ T Lymphocyte Infiltrations Are Associated with the Pathogenesis of Colorectal Cancer but Not with the Overall Survival of Patients

Tumor-infiltrating lymphocytes include heterogeneous populations of T lymphocytes that play crucial roles in the tumor immune response; importantly, their presence in the tumor tissue may predict clinical outcomes. Therefore, we herein studied the prognostic significance of the presence and location of CD3+, CD8+, and FoxP3+ T lymphocytes in colorectal cancer samples. In the intratumor analysis, our data did not reveal any association between lymphocyte infiltrations with clinical or pathological data. However, in the tumor margins, we found that the presence of high infiltrations of CD3+, CD8+, or FoxP3+ T lymphocytes were associated with TNM stages I-II (p = 0.021, p = 0.022, and p = 0.012, respectively) and absence of lymph node metastases (p = 0.010, p = 0.003, and p = 0.004, respectively). Despite these associations with good prognostic indicators, we were not able to find any statistically significant alterations in the overall survival of the patients, even though high infiltrations of FoxP3+ T lymphocytes in the tumor margins resulted in an increased overall survival of 14 months. Taken together, these data show that the presence of CD3+, CD8+, or FoxP3+T lymphocyte infiltrates in the tumor margins are associated with the pathogenesis of CRC, but only high Foxp3+ T lymphocyte infiltrations in the tumor invasive margins are inclined to indicate favorable prognosis.

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Prognostic Significance of Tumor-Infiltrating Lymphocytes for Patients With Colorectal Cancer

Archives of Surgery ◽

10.1001/archsurg.2012.35 ◽

2012 ◽

Vol 147 (4) ◽

pp. 366 ◽

Cited By ~ 83

Author(s):

Jae Hyuk Lee

Keyword(s):

Colorectal Cancer ◽

Prognostic Significance ◽

Tumor Infiltrating Lymphocytes ◽

Infiltrating Lymphocytes

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High expression of PD-L1 Predicts Worse Overall Survival in the Cavitary Lung Adenocarcinoma

10.21203/rs.3.rs-131097/v1 ◽

2020 ◽

Author(s):

Jiangyong Liu ◽

Mingming Gu ◽

Yang Xue ◽

Yong Ren ◽

Wencai Huang

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Lung Adenocarcinoma ◽

Prognostic Significance ◽

Tumor Infiltrating Lymphocytes ◽

Good Prognosis ◽

High Expression ◽

Quantitative Immunofluorescence ◽

L1 Protein ◽

Infiltrating Lymphocytes

Abstract Objective Solitary cavitary lung cancer is one of the rare types of lung cancer. Generally, the relationship between cavitary lung adenocarcinoma and immunotherapy remains unknown. We aimed to assess programmed cell death ligand-1(PD-L1) expression and CD8-positive (CD8+) tumor infiltrating lymphocytes (TILs) density, and evaluate their prognostic significance of patients with cavitary lung adenocarcinoma (LUAD). Methods 65 patients diagnosed as solitary cavitary LUAD were included in this study, 30 cases of noncavitary LUAD patients were collected as controls, and their specimens from surgery or biopsy were obtained. Expression of PD-L1 protein and CD8+ TILs were detected by traditional immunohistochemistry and multiplex quantitative immunofluorescence technology. The correlations of PD-L1 expression and clinicopathological features, including overall survival in cavitary LUAD patients was evaluated based on the follow-up data. Results Overexpression of PD-L1 protein was detected in the tumor tissues of cavitary LUAD patients compared to the noncavitary LUAD controls. PD-L1 expression level was significantly related to the lymph node (P = 0.001), TNM stage (P = 0.024), and CD8+ TIL status (rs= -0.272, P = 0.025). High PD-L1 expression predicted high mortality rate (P < 0.001), but CD8+ TIL group showed better survival in cavitary LUAD patients (P = 0.011). This phenotype with high PD-L1 expression and low CD8 + TIL predicted poorer overall survival of the patients with cavitary LUAD, compared to the other phenotypes. Moreover, CD8+ TIL was an independent good prognosis factor. Conclusion We firstly demonstrated that PD-L1 is upregulated in the cavitary LUAD patients, and high expression of PD-L1 negatively correlated with CD8 T cell infiltrating status. High PD-L1 expression and low CD8 + TIL can predict poorer overall survival of the patients with cavitary LUAD.

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Progression on the Roles and Mechanisms of Tumor-Infiltrating T Lymphocytes in Patients With Hepatocellular Carcinoma

Frontiers in Immunology ◽

10.3389/fimmu.2021.729705 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xiaoqin Zheng ◽

Wenjie Jin ◽

Shanshan Wang ◽

Huiguo Ding

Keyword(s):

Hepatocellular Carcinoma ◽

T Lymphocytes ◽

T Lymphocyte ◽

Primary Liver Cancer ◽

Tumor Resection ◽

Tumor Infiltrating Lymphocytes ◽

High Recurrence Rate ◽

Targeted Agents ◽

Poor Survival ◽

Infiltrating Lymphocytes

Primary liver cancer (PLC) is one of the most common malignancies in China, where it ranks second in mortality and fifth in morbidity. Currently, liver transplantation, hepatic tumor resection, radiofrequency ablation, and molecular-targeted agents are the major treatments for hepatocellular carcinoma (HCC). Overall, HCC has a poor survival rate and a high recurrence rate. Tumor-infiltrating lymphocytes (TILs) have been discovered to play essential roles in the development, prognosis, and immunotherapy treatment of HCC. As the major component cells of TILs, T cells are also proved to show antitumor and protumor effects in HCC. Foxp3+, CD8+, CD3+, and CD4+ T lymphocytes are the broadly studied subgroups of TILs. This article reviews the roles and mechanisms of different tumor-infiltrating T lymphocyte subtypes in HCC.

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The integration of proportion and cell counts of stromal, not intratumoral, PD-1+ tumor-infiltrating lymphocytes has prognostic significance in esophageal squamous cell carcinoma

Diseases of the Esophagus ◽

10.1093/dote/doaa035 ◽

2020 ◽

Author(s):

Qingkun Song ◽

Feng Shi ◽

Shuo Xiao ◽

Yuchen Li ◽

Yanjie Zhao ◽

...

Keyword(s):

Overall Survival ◽

Esophageal Cancer ◽

Cancer Patients ◽

Prognostic Significance ◽

Disease Free Survival ◽

Tumor Infiltrating Lymphocytes ◽

High Power Field ◽

Prognostic Effect ◽

Cell Counts ◽

Infiltrating Lymphocytes

Summary The present study aimed to investigate the prognostic effect of intratumoral and stromal exhausted tumor-infiltrating lymphocytes (TILs) on operable esophageal cancer patients. We performed a retrospective cohort study by consecutively recruiting 142 patients with esophageal cancer. The proportion and cell counts of intratumoral and stromal PD-1+ TILs in tumor microenvironment were independently evaluated by two pathologists. Neither proportion nor cell counts of intratumoral PD-1+ TILs was associated with prognosis (p > 0.05). However, patients with the proportion of stromal PD1+ TILs >20% had the median overall survival (OS) at 19 months, significantly longer than those with the proportion = 20%. The adjusted hazard ratio (HR) was 1.49 (95%CI 0.82, 2.69). Patients with cell counts of stromal PD1+ TILs = 18/ high-power field (HPF) had the median disease-free survival (DFS) at 10 months. However, patients with cell counts>18/HPF had the median DFS at 48 months (p = 0.037), and the adjusted HR was 0.59 (95%CI 0.35, 1.01). Compared with patients with proportion = 20% and cell counts >18/HPF of stromal PD1+ TILs, patients with proportion = 20% and cell counts = 18/HPF, proportion >20% and cell counts >18/HPF, and proportion >20% and cell counts = 18/HPF, had the adjusted HRs increased to 3.73, 3.36 and 3.99 for DFS (p for trend being 0.030) and the adjusted HRs increased to 2.95, 3.64 and 3.82 (p for trend being 0.015) for OS, respectively. The integration of proportion and cell counts of PD-1+ stromal TILs has a significant association with the relapse and overall survival of esophageal cancer patients. Further prospective studies are warranted.

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Overexpression of an Immune Checkpoint (CD155) in Breast Cancer Associated with Prognostic Significance and Exhausted Tumor-Infiltrating Lymphocytes: A Cohort Study

Journal of Immunology Research ◽

10.1155/2020/3948928 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Yu-Chen Li ◽

Quan Zhou ◽

Qing-Kun Song ◽

Rui-Bin Wang ◽

Shuzhen Lyu ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Cohort Study ◽

Tumor Cells ◽

Immune Checkpoint ◽

Prognostic Significance ◽

Tumor Infiltrating Lymphocytes ◽

Immune Microenvironment ◽

Infiltrating Lymphocytes ◽

Low Expression

Purpose. The immune checkpoint inhibitor is approved for breast cancer treatment, but the low expression of PD-L1 limits the immunotherapy. CD155 is another immune checkpoint protein in cancers and interacts with ligands to regulate immune microenvironment. This study is aimed at investigating the expression of CD155 and the association with prognosis and pathological features of breast cancer. Methods. 126 patients were recruited this cohort study consecutively, and CD155 expression on tumor cells was detected by immunohistochemistry. The Kaplan-Meier survival curve and Cox hazard regression model were used to estimate the association. Results. 38.1% patients had an overexpression of CD155, and the proportion of tumor cells with CD155 overexpression was 17%, 39%, 37%, and 62% among Luminal A, Luminal B, HER2-positive, and triple negative breast cancer cases, respectively (p<0.05). Patients with CD155 overexpression had the Ki-67 index significantly higher than that of patients with low expression (42% vs. 26%). Though the number of tumor-infiltrating lymphocytes was higher among patients with CD155 overexpression (144/HPF vs. 95/HPF), the number of PD-1+ lymphocytes was significantly higher (52/HPF vs. 25/HPF, p<0.05). Patients of CD155 overexpression had the disease-free and overall survival decreased by 13 months and 9 months, respectively (p<0.05). CD155 overexpression was associated with an increased relapse (HR=13.93, 95% CI 2.82, 68.91) and death risk for breast cancer patients (HR=5.47,1.42,20.99). Conclusions. Overexpression of CD155 was correlated with more proliferative cancer cells and a dysfunctional immune microenvironment. CD155 overexpression introduced a worse relapse-free and overall survival and might be a potential immunotherapy target for breast cancer.

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Review for "Relationship between T cell receptor clonotype and PD‐1 expression of tumor‐infiltrating lymphocytes in colorectal cancer"

10.1002/eji.201948399/v2/review1 ◽

2020 ◽

Author(s):

Lei Zhang

Keyword(s):

Colorectal Cancer ◽

T Cell ◽

T Cell Receptor ◽

Tumor Infiltrating Lymphocytes ◽

Cell Receptor ◽

Infiltrating Lymphocytes

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Improving Risk Stratification of Early Oral Tongue Cancer with TNM-Immune (TNM-I) Staging System

Cancers ◽

10.3390/cancers13133235 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3235

Author(s):

Alhadi Almangush ◽

Ibrahim O. Bello ◽

Ilkka Heikkinen ◽

Jaana Hagström ◽

Caj Haglund ◽

...

Keyword(s):

Overall Survival ◽

Tongue Cancer ◽

Early Stage ◽

Disease Free Survival ◽

Tumor Infiltrating Lymphocytes ◽

Staging System ◽

Oral Tongue ◽

Oral Tongue Cancer ◽

Important Player ◽

Infiltrating Lymphocytes

Although patients with early-stage oral tongue squamous cell carcinoma (OTSCC) show better survival than those with advanced disease, there is still a number of early-stage cases who will suffer from recurrence, cancer-related mortality and worse overall survival. Incorporation of an immune descriptive factor in the staging system can aid in improving risk assessment of early OTSCC. A total of 290 cases of early-stage OTSCC re-classified according to the American Joint Committee on Cancer (AJCC 8) staging were included in this study. Scores of tumor-infiltrating lymphocytes (TILs) were divided as low or high and incorporated in TNM AJCC 8 to form our proposed TNM-Immune system. Using AJCC 8, there were no significant differences in survival between T1 and T2 tumors (p > 0.05). Our proposed TNM-Immune staging system allowed for significant discrimination in risk between tumors of T1N0M0-Immune vs. T2N0M0-Immune. The latter associated with a worse overall survival with hazard ratio (HR) of 2.87 (95% CI 1.92–4.28; p < 0.001); HR of 2.41 (95% CI 1.26–4.60; p = 0.008) for disease-specific survival; and HR of 1.97 (95% CI 1.13–3.43; p = 0.017) for disease-free survival. The TNM-Immune staging system showed a powerful ability to identify cases with worse survival. The immune response is an important player which can be assessed by evaluating TILs, and it can be implemented in the staging criteria of early OTSCC. TNM-Immune staging forms a step towards a more personalized classification of early OTSCC.

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Predicted CD4+ T cell infiltration levels could indicate better overall survival in sarcoma patients

Journal of International Medical Research ◽

10.1177/0300060520981539 ◽

2021 ◽

Vol 49 (1) ◽

pp. 030006052098153

Author(s):

Qing Bi ◽

Yang Liu ◽

Tao Yuan ◽

Huizhen Wang ◽

Bin Li ◽

...

Keyword(s):

Overall Survival ◽

T Cell ◽

Survival Data ◽

Tumor Infiltrating Lymphocytes ◽

The Cancer Genome Atlas ◽

Cell Infiltration ◽

T Cell Infiltration ◽

Whole Exome ◽

Cancer Genome Atlas ◽

Infiltrating Lymphocytes

Objective The role of tumor-infiltrating lymphocytes (TILs) has not yet been characterized in sarcomas. The aim of this bioinformatics study was to explore the effect of TILs on sarcoma survival and genome alterations. Methods Whole-exome sequencing, transcriptome sequencing, and survival data of sarcoma were obtained from The Cancer Genome Atlas. Immune infiltration scores were calculated using the Tumor Immune Estimation Resource. Potential associations between abundance of infiltrating TILs and survival or genome alterations were examined. Results Levels of CD4+ T cell infiltration were associated with overall survival of patients with pan-sarcomas, and higher CD4+ T cell infiltration levels were associated with better survival. Somatic copy number alterations, rather than mutations, were found to correlate with CD4+ T cell infiltration levels. Conclusions This data mining study indicated that CD4+ T cell infiltration levels predicted from RNA sequencing could predict sarcoma prognosis, and higher levels of CD4+ T cells infiltration indicated a better chance of survival.

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