Tumor-Infiltrating Immune Cells Are Associated With Prognosis of Gastric Cancer

Li, Kai; Yang, Kun; Wu, Bin; Chen, Hai‐Ning; Chen, Xiaolong; Jiang, Lili; Ye, Fuxiang; He, Du; Lu, Zheng-Hao; Xue, Ling; Zhang, WeiHan; Qiu, Li; Zhou, Zong‐Guang; Mo, XianMing; Hu, Jian-Kun

doi:10.1097/md.0000000000001631

Cited by 95 publications

(90 citation statements)

References 47 publications

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“…In Fig 2E we have compared these results of our numerical simulation with experimental data obtained from various literatures. Here, we clearly observe that our simulation corroborates very well with the experimental observations made from blood samples of Cancer patients (Fig 2E) [36, 37]. Additionally, we have observed the changes in the T H1 :T H2 and M1:M2 ratios that have important implications in Cancer prognosis.…”

Section: Resultssupporting

confidence: 89%

Exploring immuno-regulatory mechanisms in the tumor microenvironment: Model and design of protocols for cancer remission

Ganguli

Sarkar

2018

PLoS ONE

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The tumor microenvironment comprising of the immune cells and cytokines acts as the ‘soil’ that nourishes a developing tumor. Lack of a comprehensive study of the interactions of this tumor microenvironment with the heterogeneous sub-population of tumor cells that arise from the differentiation of Cancer Stem Cells (CSC), i.e. the ‘seed’, has limited our understanding of the development of drug resistance and treatment failures in Cancer. Based on this seed and soil hypothesis, for the very first time, we have captured the concept of CSC differentiation and tumor-immune interaction into a generic model that has been validated with known experimental data. Using this model we report that as the CSC differentiation shifts from symmetric to asymmetric pattern, resistant cancer cells start accumulating in the tumor that makes it refractory to therapeutic interventions. Model analyses unveiled the presence of feedback loops that establish the dual role of M2 macrophages in regulating tumor proliferation. The study further revealed oscillations in the tumor sub-populations in the presence of TH1 derived IFN-γ that eliminates CSC; and the role of IL10 feedback in the regulation of TH1/TH2 ratio. These analyses expose important observations that are indicative of Cancer prognosis. Further, the model has been used for testing known treatment protocols to explore the reasons of failure of conventional treatment strategies and propose an improvised protocol that shows promising results in suppressing the proliferation of all the cellular sub-populations of the tumor and restoring a healthy TH1/TH2 ratio that assures better Cancer remission.

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Section: Resultssupporting

confidence: 89%

Exploring immuno-regulatory mechanisms in the tumor microenvironment: Model and design of protocols for cancer remission

Ganguli

Sarkar

2018

PLoS ONE

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“…Infiltration by CD3 + and CD8 + T cells [92,93], CD20 + B cells [94] and expression of the chemokine receptor CXCR3 [95] have been reported to correlate with improved prognosis. Conflicting results have been seen for FOXP3 + T regs , which in some studies are associated with improved prognosis [96,97], and in others, a worse prognosis [98,99]. Expression of the chemokine receptor CCR7 [99] and immune checkpoint molecule PD-L1 [100] have also been associated with worse prognosis in gastric cancer.…”

Section: Tils In Upper Gastrointestinal Tract Carcinomasmentioning

confidence: 99%

Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non–Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors

Hendry

Salgado

Gevaert

et al. 2017

Advances in Anatomic Pathology

534

330

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Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies are evaluated and implemented in different tumor types. However, many different approaches can be used to assess and describe the immune response, which limits efforts at implementation as a routine clinical biomarker. In part 1 of this review, we have proposed a standardized methodology to assess tumor infiltrating lymphocytes (TILs) in solid tumors, based on the International Immuno-Oncology Biomarkers Working Group guidelines for invasive breast carcinoma. In part 2 of this review, we discuss the available evidence for the prognostic and predictive value of TILs in common solid tumors, including carcinomas of the lung, gastrointestinal tract, genitourinary system, gynecological system, and head and neck, as well as primary brain tumors, mesothelioma and melanoma. The particularities and different emphases in TIL assessment in different tumor types are discussed. The standardized methodology we propose can be adapted to different tumor types and may be used as a standard against which other approaches can be compared. Standardization of TIL assessment will help clinicians, researchers and pathologists to conclusively evaluate the utility of this simple biomarker in the current era of immunotherapy.

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“…CD8 is mainly expressed on cytotoxic T lymphocytes (CTLs) which could specifically kill tumor cells in anti-tumor immune responses [42]. Soluble tumor antigens from tumor cells are captured by antigen presenting cells (APCs), and then combined with major histocompatibility complex (MHC) class I molecules into complex which expressed on APCs.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Role of Tumor-Infiltrating Lymphocytes in Esophagus Cancer: a Meta-Analysis

Zheng¹,

Song

Shao

et al. 2018

Cell Physiol Biochem

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Background/Aims: Several studies have verified the correlation between tumor-infiltrating lymphocytes (TILs) and survival of patients with esophagus cancer (EC). However, the prognostic role of TILs is still controversial. Therefore, we performed this meta-analysis. Methods: We searched PubMed, Embase and the Cochrane Library (last update by August 30, 2017) to identify studies assessing the effect of TILs on survival of patients with EC. Pooled hazard ratios (HRs) for overall survival (OS), disease-free survival (DFS) and cancer specific survival (CSS) were estimated using fixed-effects models or random-effects models, which depends on the heterogeneity. Results: Data from 22 observational studies including 2909 patients were summarized. Pooled analysis indicated that generalized TILs were favorable prognostic markers for OS in patients with EC (pooled HR = 0.48; 95% CI = 0.38-0.61; P < 0.001). For TIL subsets, CD8⁺ TILs were associated with improved OS (pooled HR = 0.68; 95% CI = 0.58–0.84; P < 0.001) and DFS (pooled HR = 0.90; 95% CI = 0.85-0.95; P < 0.001); FoxP3⁺ TILs were associated with patients’ DFS (pooled HR = 0.88; 95% CI = 0.81-0.96; P = 0.003). High CD57⁺ TILs indicated a better OS in patients with EC (pooled HR = 0.50; 95% CI = 0.35-0.72; P < 0.001). In addition, the pooled results showed that other TIL subsets including CD3⁺, CD4⁺ and CD45RO⁺ TILs were not associated with patients’ survival (P > 0.05). Conclusions: For patients with EC, some TIL subsets could serve as prognostic biomarkers. The application of TILs in the immunotherapy of EC needs to be verified through a large amount of clinical research.

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Tumor-Infiltrating Immune Cells Are Associated With Prognosis of Gastric Cancer

Cited by 95 publications

References 47 publications

Exploring immuno-regulatory mechanisms in the tumor microenvironment: Model and design of protocols for cancer remission

Exploring immuno-regulatory mechanisms in the tumor microenvironment: Model and design of protocols for cancer remission

Prognostic Role of Tumor-Infiltrating Lymphocytes in Esophagus Cancer: a Meta-Analysis

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