Prognostic value of tumor-infiltrating lymphocytes in Epstein–Barr virus-associated gastric cancer

Kang, Byung Woog; Seo, An Na; Yoon, Sam S.; Bae, Han Ik; Jeon, Seong Woo; Kwon, Oh Kyoung; Chung, Ho Young; Yu, Wansik; Kang, Hyunwoo; Kim, J.G.

doi:10.1093/annonc/mdv610

Cited by 129 publications

(125 citation statements)

References 29 publications

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“…This demonstrates that immune escape mechanism mediated by PD-1 may play an even broader and crucial role in EBV+GC. Furthermore, some previous study demonstrated that more TILs were present in EBV+ GC [41][42][43]. And patients with the lymphoepithelioma-like carcinoma (LELC) subtype had better OS and DFS than patients with the other subtypes.…”

Section: Discussionmentioning

confidence: 99%

The PD-1, PD-L1 expression and CD3+ T cell infiltration in relation to outcome in advanced gastric signet-ring cell carcinoma, representing a potential biomarker for immunotherapy.

Jin

et al. 2017

JCO

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Section: Discussionmentioning

confidence: 99%

The PD-1, PD-L1 expression and CD3+ T cell infiltration in relation to outcome in advanced gastric signet-ring cell carcinoma, representing a potential biomarker for immunotherapy.

Jin

et al. 2017

JCO

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“…The anti-tumorigenic properties of immune cells (T-, as well as B-lymphocytes) are well-established and high levels of TILs are commonly associated with improved survival in a variety of tumors, including gastric carcinomas (2,23).…”

Section: Discussionmentioning

confidence: 99%

High Density of Tumor-infiltrating B-Lymphocytes and Plasma Cells Signifies Prolonged Overall Survival in Adenocarcinoma of the Esophagogastric Junction

Knief

Reddemann

Petrova

et al. 2016

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Abstract. Background: Tumor-infiltrating lymphocytes (TILs) have been shown to be of prognostic significance in a variety of tumors. Not only T-cell, but also B-cell In recent years, studies concerning the microenvironment of tumors, especially tumor-infiltrating lymphocytes (TILs), have been abundant. This microenvironment has been shown to influence overall survival (OS), as well as relapse times, and probability of tumor recurrence (1, 2). However, most studies have focused on the relationship between T-cell infiltration and patients' outcome, while the role of tumor infiltrating B-lymphocytes (TIL-Bs), as well as plasma cells in this setting, is still poorly understood and less commonly investigated.Not only the presence, but also the distribution pattern has been described as being crucial to prognosis: In carcinomas, immune cells are predominantly found in the stroma (3) and the formation of dense, follicle-like lymphocyte infiltrates (so-called tertiary lymphatic structures (TLSs), which arise in non-lymphoid tissues, often in the context of chronic inflammation) has been reported to have the strongest impact on prognosis and survival (2, 4, 5).T-lymphocytes (especially cytotoxic T-cells), as well as Blymphocytes, increase and establish the activation of antitumoral immunity (as an adaptive mechanism), leading to increased cell death in tumors and resulting in improved prognosis in patients with high levels of TILs (2, 6). Tumorassociated plasma cells have been described to have a significant impact on prognosis through modulation of the humoral immune response (7).Up to date, most reports in the literature state a positive effect of TILs in respect to OS, relapse-free survival and association with favorable prognostic factors, as well as lower T-stage (8). High B-cell density is said to be associated with improved outcome in gastric, breast and colorectal cancer (9-11), as well as squamous cell carcinoma of the tongue (12), melanoma and hepatocellular carcinoma (5, 13). The same correlation has been shown for pancreatic adenocarcinomas, though here the impact was only measurable if cells were arranged in the pattern of TLSs (4,14). High proportions of TILs have also been shown to be predictive of response to neoadjuvant therapy in breast cancer patients (15). 5339

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“…Kang et al [90] assessed the prognostic value of TILs amongst EBV-associated gastric carcinomas using a modification of the International Immuno-Oncology Biomarkers Working Group guidelines for breast carcinoma [1]. sTILs were found to be an independent prognostic factor for recurrence free survival but not overall survival, while iTILs were not significantly associated with either recurrence free or overall survival [90]. Giamperi et al used a similar approach and found that sTILs were significantly associated with dMMR status, but that both sTILs and dMMR status were independent favorable prognostic factors in a multivariate model [91].…”

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

571

366

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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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Prognostic value of tumor-infiltrating lymphocytes in Epstein–Barr virus-associated gastric cancer

Abstract: The histologic subclassification and TILs can be used to predict RFS and DFS for patients with EBVaGC.

Cited by 129 publications

References 29 publications

The PD-1, PD-L1 expression and CD3+ T cell infiltration in relation to outcome in advanced gastric signet-ring cell carcinoma, representing a potential biomarker for immunotherapy.

The PD-1, PD-L1 expression and CD3+ T cell infiltration in relation to outcome in advanced gastric signet-ring cell carcinoma, representing a potential biomarker for immunotherapy.

High Density of Tumor-infiltrating B-Lymphocytes and Plasma Cells Signifies Prolonged Overall Survival in Adenocarcinoma of the Esophagogastric Junction

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