Clinicopathological features of programmed death ligand 1 expression with tumor-infiltrating lymphocyte, mismatch repair, and Epstein–Barr virus status in a large cohort of gastric cancer patients

Kawazoe, Akihito; Kuwata, Takeshi; Kuboki, Yasutoshi; Shitara, Kohei; Nagatsuma, Akiko Kawano; Aizawa, Masaaki; Yoshino, Takayuki; Doi, Toshihiko; Ohtsu, Atsushi; Ochiai, Atsushi

doi:10.1007/s10120-016-0631-3

Cited by 194 publications

(197 citation statements)

References 22 publications

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“…A review of the investigation of TILs I gynecologic cancers revealed that most of the cases that had positive intramural CD3/ CD8 had better chemotherapeutic and/or surgical outcomes [17], supporting an effective interaction between the host's immune system and cancer. Additionally, a report on gastric cancers revealed that programmed cell death-1 ligand 1-positive tumors had an increased density of TILs, and were frequently observed in mismatch repair deficiency subtype [18]. Although detailed mechanisms are still undetermined, TILs and zone formation of LI could be associated with immune response in the host and inverse effects for prognoses.…”

Section: Discussionmentioning

confidence: 99%

Zone Formation of Lymphocyte Infiltration at Invasive Front as a Biomarker of Prognosis in Endometrial Carcinomas

et al. 2018

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Objective: The clinical significance of lymphocyte infiltration (LI) at the invasive front in endometrial carcinomas (EC) has not been determined. The aim of the current study was to evaluate the association between zone formation of LI at the invasive front of the tumor margin and prognoses of the patients with EC. Methods: All available pathological slides of the enrolled cases were reviewed, and the degree of LI at the invasive front was categorized into 2 groups: strong LI and weak LI. Clinical significance of LI was evaluated retrospectively. Results: A total of 333 cases with EC were enrolled in the study: 225 cases with weak LI and 108 cases with strong LI. Weak LI was more frequently observed in the patients with grade1/2 endometrioid EC. Multivariate analyses for progression-free survival (PFS) and overall survival (OS) revealed that weak LI was identified as an independent worse prognostic factor for OS (p = 0.004) in addition to PFS (p = 0.022). Conclusion: Weak LI at the invasive front of the tumor margin was associated with worse prognoses in EC. Although further studies are needed, it is suggested that LI could be a biomarker of prognoses in EC.

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Section: Discussionmentioning

confidence: 99%

Zone Formation of Lymphocyte Infiltration at Invasive Front as a Biomarker of Prognosis in Endometrial Carcinomas

et al. 2018

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“…Several studies have demonstrated that PD-L1 immunoexpression is heterogeneous in GC, as in other tumour models. PD-L1 overexpression is associated with high densities of CD3+ and CD8+ tumour-infiltrating lymphocytes [67][68][69], GC with lymphoid stroma morphology [70], and both an EBV+ and MSI-high molecular status [69,[71][72][73][74]. However, the correlation with PD-L1 amplification, prognosis, and response to targeted immunotherapies is still debated and deserves further study.…”

Section: Moving Towards Molecular Subtyping and Precision Medicinementioning

confidence: 99%

Heterogeneity in Gastric Cancer: From Pure Morphology to Molecular Classifications

Gullo

Carneiro²,

Oliveira³

et al. 2017

Pathobiology

111

103

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Gastric cancer (GC) represents a global health concern. Despite advances in prevention, diagnosis, and therapy, GC is still the third leading cause of cancer mortality worldwide, with more than 720,000 estimated deaths in 2012. Overall survival for advanced disease is about 1 year, a dismal prognosis that is partly due to the high levels of biological heterogeneity found in GC. Indeed, GC is a highly heterogeneous disease from morphological and molecular standpoints. The numerous histological and molecular classifications currently available reflect such heterogeneity. Although recent high-throughput studies cluster the molecular data obtained into subgroups with clinical relevance, we still need a practical, prognostic, and predictive classification system, integrating morphological and molecular features, towards the identification of novel therapeutic targets. It is noteworthy that GC heterogeneity encompasses not only interpatient variability (intertumour heterogeneity), but also variations within the same tumour (intratumour heterogeneity). The latter encompasses spatial heterogeneity (in different tumour areas) and temporal heterogeneity (along progression from primary to recurrent and/or metastatic disease). In this review, we analyse the morphological, immunophenotypic, and molecular heterogeneity in GC as the basis for a better understanding of the disease, and discuss the practical implications for diagnostic pathology, prognostic evaluation, and precision therapy.

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“…PD‐L1 and PD‐L2 ligate the inhibitory T‐cell receptor PD‐1, which abrogates the T‐cell‐mediated immune response . Overall, 25‐65% of all gastric cancers express PD‐L1, which is associated with worse pathologic features and clinical outcomes . Patterns of PD‐L1 expression on tumor and immune cells and density of the immune infiltrate is associated with T category, rate of lymph node metastasis, and disease‐free survival, however, these findings require further confirmation.…”

Section: Biologic Rationale For Immunotherapy Efficacy In Gastric Canmentioning

confidence: 99%

“…PD‐L1 is a co‐inhibitory molecule expressed on the surface of tumor‐infiltrating macrophages, antigen‐presenting cells, and the tumor cells of approximately half of gastric cancers . PD‐L1 is a ligand for the inhibitory T‐cell receptor PD‐1, which induces T‐cell exhaustion, apoptosis, and anergy .…”

Section: Principles Of Checkpoint Blockade Immunotherapymentioning

confidence: 99%

Checkpoint blockade in esophagogastric cancer

Cohen

Strong

Janjigian

2018

Journal of Surgical Oncology

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There are few effective treatment options for metastatic esophagogastric adenocarcinomas after progression on second-line chemotherapy. Immune checkpoint blockade therapy is a promising treatment strategy for selected advanced esophagogastric cancer, and the PD-1 inhibitor pembrolizumab has recently been approved for metastatic or recurrent gastric or gastroesophageal junction cancer that has progressed beyond second-line systemic therapy. We review the current data supporting immune checkpoint blockade therapy in advanced esophagogastric adenocarcinoma.

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Clinicopathological features of programmed death ligand 1 expression with tumor-infiltrating lymphocyte, mismatch repair, and Epstein–Barr virus status in a large cohort of gastric cancer patients

Abstract: In GC, PD-L1 expression was associated with distinct clinicopathological features, including high densities of TILs, MMR deficiency, and EBV positivity, but was not a prognostic factor.

Cited by 194 publications

References 22 publications

Zone Formation of Lymphocyte Infiltration at Invasive Front as a Biomarker of Prognosis in Endometrial Carcinomas

Zone Formation of Lymphocyte Infiltration at Invasive Front as a Biomarker of Prognosis in Endometrial Carcinomas

Heterogeneity in Gastric Cancer: From Pure Morphology to Molecular Classifications

Checkpoint blockade in esophagogastric cancer

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