Programmed Death Ligand 1: A Step Toward Immunoscore for Esophageal Cancer

Hynes, Conor F.; Kwon, Dong Hyang; Vadlamudi, Chaitanya; Lofthus, Alexander; Iwamoto, Akira; Chahine, Joeffrey J.; Desale, Sameer; Margolis, Marc; Kallakury, Bhaskar; Watson, Thomas J.; Haddad, Nadim; Marshall, M. Blair

doi:10.1016/j.athoracsur.2018.05.002

Cited by 13 publications

(9 citation statements)

References 22 publications

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“…For PD-L1, a well-defined immune checkpoint marker, conflicting data exist in EAC. This is among other things due to different analysis and especially scoring methods used in the past [ 21 , 22 ]. The combined positive score (CPS) for PD-L1 was established for gastric and gastroesophageal junction adenocarcinomas serving as a predictive marker for PD1-inhibitor therapy [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Distribution of tumor-infiltrating-T-lymphocytes and possible tumor-escape mechanisms avoiding immune cell attack in locally advanced adenocarcinomas of the esophagus

et al. 2021

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Introduction The inflammatory microenvironment has emerged as one of the focuses of cancer research. Little is known about the immune environment in esophageal adenocarcinoma (EAC) and possible tumor-escape mechanisms to avoid immune cell attack. Patients and methods We measured T cell inflammation (CD3, CD8) in the microenvironment using a standardized software-based evaluation algorithm considering different predefined tumor areas as well as expression of MHC class 1 and PD-L1 on 75 analyzable primarily resected and locally advanced (≥ pT2) EACs. We correlated these findings statistically with clinical data. Results Patients with high amounts of T cell infiltration in their tumor center showed a significant survival benefit of 41.4 months compared to 16.3 months in T cell poor tumors (p = 0.025), although CD3 fails to serve as an independent prognostic marker in multivariate analysis. For the invasion zone, a correlation between number of T-cells and overall survival was not detectable. Loss of MHC1 protein expression on tumor cells was seen in 32% and PD-L1 expression using the combined positive score (CPS) in 21.2%. Most likely due to small numbers of cases, both markers are not prognostically relevant, even though PD-L1 expression correlates with advanced tumor stages. Discussion Our analyses reveal an outstanding, though not statistically independent, prognostic relevance of T-cell-rich inflammation in our group of EACs, in particular driven by the tumor center. For the first time, we describe that the inner part of the invasion zone in EACs shows significantly fewer T-cells than other tumor segments and is prognostically irrelevant. We also demonstrate that the loss of antigen presenting ability via MHC1 downregulation by the carcinoma cells is a common escape mechanism in EACs. Future work will need to show whether tumors with MHC class 1 loss respond less well to immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Distribution of tumor-infiltrating-T-lymphocytes and possible tumor-escape mechanisms avoiding immune cell attack in locally advanced adenocarcinomas of the esophagus

et al. 2021

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“…In a clinical trial of SHR-1210, an anti-PD-1 antibody, Huang et al showed that PD-L1 expression was not significantly correlated with ORR in patients with EC (129). Hynes et al verified that in patients with EAC, survival outcomes were worse in patients whose tumors stained positive for PD-L1 than in patients with PD-L 1 -n e g a t i v e t u m o r s w h o u n d e r w e n t n e o a d j u v a n t chemoradiation therapy (130). In addition, Ohigashi et al observed that even in patients with ESCC, PD-L1-positive patients exhibited a poorer prognosis, and upregulation of PD-L1 was more pronounced, with worse tumor differentiation, positive lymph node metastasis, and advanced stage of ESCC (131), indicating that PD-L1 status may be a negative predictor of prognosis for patients with EC.…”

Section: Immune Checkpoint Proteinsmentioning

confidence: 99%

Immunotherapy resistance in esophageal cancer: Possible mechanisms and clinical implications

et al. 2022

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Esophageal cancer (EC) is a common malignant gastrointestinal (GI) cancer in adults. Although surgical technology combined with neoadjuvant chemoradiotherapy has advanced rapidly, patients with EC are often diagnosed at an advanced stage and the five-year survival rate remains unsatisfactory. The poor prognosis and high mortality in patients with EC indicate that effective and validated therapy is of great necessity. Recently, immunotherapy has been successfully used in the clinic as a novel therapy for treating solid tumors, bringing new hope to cancer patients. Several immunotherapies, such as immune checkpoint inhibitors (ICIs), chimeric antigen receptor T-cell therapy, and tumor vaccines, have achieved significant breakthroughs in EC treatment. However, the overall response rate (ORR) of immunotherapy in patients with EC is lower than 30%, and most patients initially treated with immunotherapy are likely to develop acquired resistance (AR) over time. Immunosuppression greatly weakens the durability and efficiency of immunotherapy. Because of the heterogeneity within the immune microenvironment and the highly disparate oncological characteristics in different EC individuals, the exact mechanism of immunotherapy resistance in EC remains elusive. In this review, we provide an overview of immunotherapy resistance in EC, mainly focusing on current immunotherapies and potential molecular mechanisms underlying immunosuppression and drug resistance in immunotherapy. Additionally, we discuss prospective biomarkers and novel methods for enhancing the effect of immunotherapy to provide a clear insight into EC immunotherapy.

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“…16 Similar results have also been achieved by Hynes et al in their study where PD-L1 positivity was found to be associated with significantly lower survival in specimens of patients who underwent esophagectomies for EAC. 17 More recently, Rong et al, 18 using tissue microarray and immunohistochemistry, studied PD-L1 expression on tumor cells and tumor-infiltrating cell in 378 advanced (T2-T4a) ESCC. No patient recruited had undergone neoadjuvant chemotherapy that could have changed PD-L1 exposure.…”

Section: Immunomodulation Mechanisms and Immune-checkpoint Expressionmentioning

confidence: 99%

Synergism Between Immunotherapy and Radiotherapy in Esophageal Cancer: An Overview of Current Knowledge and Future Perspectives

Sardaro

Ferrari

Carbonara

et al. 2021

Cancer Biotherapy and Radiopharmaceuticals

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Background: Esophageal cancer (EC) is an aggressive neoplasm of the gastrointestinal tract that is usually treated with a combination of chemotherapy, radiotherapy (RT), and/or surgery, according to disease status. Despite the availability of multimodal therapeutic strategies, local recurrence is frequently observed. Immunotherapy is a promising therapeutic approach that is currently highly investigated in association to standard therapies, including RT, with the aim to improve patients' outcomes. Materials and Methods: A PubMed search was performed with the following keywords in all fields: ''esophageal cancer'' and ''radiotherapy'' and ''radiation'' and ''immunotherapy'' and ''PD-1'' and ''PD L1.'' For an overview of ongoing trials, an additional search on ClinicalTrials.gov website was performed using the keywords ''esophageal cancer'' and ''immunotherapy'' and ''PD-L1'' and ''CTLA-4'' and ''radiation'' and ''radiotherapy.'' Emerging data from preclinical and clinical studies are suggesting a synergistic effect between immunotherapy and RT. With the aim to update the knowledge of this synergistic immune-mediated antitumor activity and discuss current challenges, the authors summarize published data concerning the basic mechanisms and the effectiveness and tolerance of the combination between immunotherapy and RT for patients with EC, followed by an overview of ongoing clinical trial. Conclusions: Published results encourage the use of personalized therapeutic approaches for EC patients in the future; results from ongoing studies will help to identify the optimal strategies for patient selection and treatment response evaluation.

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Programmed Death Ligand 1: A Step Toward Immunoscore for Esophageal Cancer

Abstract: Positive staining for PD-L1 may be a prognostic marker for decreased survival in esophageal adenocarcinoma. Additional TIL cell types should be investigated for creation of an esophageal cancer Immunoscore. PD-L1 has potential as a therapeutic target.

Cited by 13 publications

References 22 publications

Distribution of tumor-infiltrating-T-lymphocytes and possible tumor-escape mechanisms avoiding immune cell attack in locally advanced adenocarcinomas of the esophagus

Distribution of tumor-infiltrating-T-lymphocytes and possible tumor-escape mechanisms avoiding immune cell attack in locally advanced adenocarcinomas of the esophagus

Immunotherapy resistance in esophageal cancer: Possible mechanisms and clinical implications

Synergism Between Immunotherapy and Radiotherapy in Esophageal Cancer: An Overview of Current Knowledge and Future Perspectives

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