The Prognostic Value of the Lymph Node in Oesophageal Adenocarcinoma; Incorporating Clinicopathological and Immunological Profiling

Donlon, Noel E; Davern, Maria; Sheppard, Andrew; Power, Robert; O’Connell, Fiona; Heeran, Aisling B.; King, Ross; Hayes, Conall; Bhardwaj, Anshul; Phelan, J.J.; Dunne, Margaret R.; Ravi, Narayanasamy; Donohoe, Claire L.; Reynolds, John V.; Lysaght, Joanne

doi:10.3390/cancers13164005

Cited by 6 publications

(2 citation statements)

References 45 publications

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“…OAC patient-derived tumour-conditioned media (TCM) was generated as previously described [30]. OAC tumour explants of ~2-3 mm 3 were transferred into 1 mL of serumfree M199 media (Gibco, Billings, MT, USA), supplemented with gentamicin in a 12-well plate.…”

Section: Generation Of Tumour-conditioned Mediamentioning

confidence: 99%

Analysing the Combined Effects of Radiotherapy and Chemokine Receptor 5 Antagonism: Complementary Approaches to Promote T Cell Function and Migration in Oesophageal Adenocarcinoma

Davern,

O’ Donovan,

Donlon

et al. 2024

Biomedicines

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The presence of an immunosuppressive tumour microenvironment in oesophageal adenocarcinoma (OAC) is a major contributor to poor responses. Novel treatment strategies are required to supplement current regimens and improve patient survival. This study examined the immunomodulatory effects that radiation therapy and chemokine receptor antagonism impose on T cell phenotypes in OAC with a primary goal of identifying potential therapeutic targets to combine with radiation to improve anti-tumour responses. Compared with healthy controls, anti-tumour T cell function was impaired in OAC patients, demonstrated by lower IFN-γ production by CD4+ T helper cells and lower CD8+ T cell cytotoxic potential. Such diminished T cell effector functions were enhanced following treatment with clinically relevant doses of irradiation. Interestingly, CCR5+ T cells were significantly more abundant in OAC patient blood compared with healthy controls, and CCR5 surface expression by T cells was further enhanced by clinically relevant doses of irradiation. Moreover, irradiation enhanced T cell migration towards OAC patient-derived tumour-conditioned media (TCM). In vitro treatment with the CCR5 antagonist Maraviroc enhanced IFN-γ production by CD4+ T cells and increased the migration of irradiated CD8+ T cells towards irradiated TCM, suggesting its synergistic therapeutic potential in combination with irradiation. Overall, this study highlights the immunostimulatory properties of radiation in promoting anti-tumour T cell responses in OAC and increasing T cell migration towards chemotactic cues in the tumour. Importantly, the CCR5 antagonist Maraviroc holds promise to be repurposed in combination with radiotherapy to promote anti-tumour T cell responses in OAC.

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Section: Generation Of Tumour-conditioned Mediamentioning

confidence: 99%

Analysing the Combined Effects of Radiotherapy and Chemokine Receptor 5 Antagonism: Complementary Approaches to Promote T Cell Function and Migration in Oesophageal Adenocarcinoma

Davern,

O’ Donovan,

Donlon

et al. 2024

Biomedicines

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“…The burden of OAC is expected to rise dramatically and surpass oesophageal squamous cell carcinoma, in high-income countries by 2020 [3], with an accompanying rise in the number of patients seeking treatment. Curative therapy consists of surgery, either alone or in combination with adjuvant or neo-adjuvant chemotherapy or radiation, or combination chemoradiotherapy regimens (neo-CRT) [4,5]. However, only a minority of patients respond to such treatments, meaning the majority (70-80%) of patients will experience treatment-related toxicity and delay to surgery with no clinical benefit [6,7].…”

Section: Introductionmentioning

confidence: 99%

Identification of plasma proteins associated with oesophageal cancer chemotherapeutic treatment outcomes using SWATH-MS

Guo

Minas

Synowsky

et al. 2022

Preprint

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Oesophageal adenocarcinoma (OAC) is an aggressive cancer with a five-year survival of <15%. Current chemotherapeutic strategies only benefit a minority (20-30%) of patients and there are no methods available to differentiate between responders and non-responders. We performed quantitative proteomics using Sequential Window Acquisition of all THeoretical fragment-ion spectra-Mass Spectrometry (SWATH-MS) on albumin/IgG-depleted and non-depleted plasma samples from 23 patients with locally advanced OAC prior to treatment. Individuals were grouped based on tumour regression (TRG) score (TRG1/2/3 vs TRG4/5) after chemotherapy, and differentially abundant proteins were compared. Protein depletion of highly abundant proteins led to the identification of around twice as many proteins. SWATH-MS revealed significant quantitative differences in the abundance of several proteins between the two groups. These included complement c1q subunit proteins, C1QA, C1QB and C1QC, which were of higher abundance in the low TRG group. Of those that were found to be of higher abundance in the high TRG group, GSTP1 was found to exhibit the lowest p-value and highest classification accuracy and Cohen's kappa value. Concentrations of these proteins were further examined using ELISA-based assays. This study provides quantitative information relating to differences in the plasma proteome that underpin response to chemotherapeutic treatment in oesophageal cancers.

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The clinical importance of the host anti-tumour reaction patterns in regional tumour draining lymph nodes in patients with locally advanced resectable gastric cancer: a systematic review and meta-analysis

Budginaite,

Kloft,

van Kuijk

et al. 2023

Gastric Cancer

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Background The status of regional tumour draining lymph nodes (LN) is crucial for prognostic evaluation in gastric cancer (GaC) patients. Changes in lymph node microarchitecture, such as follicular hyperplasia (FH), sinus histiocytosis (SH), or paracortical hyperplasia (PH), may be triggered by the anti-tumour immune response. However, the prognostic value of these changes in GaC patients is unclear. Methods A systematic search in multiple databases was conducted to identify studies on the prognostic value of microarchitecture changes in regional tumour-negative and tumour-positive LNs measured on histopathological slides. Since the number of GaC publications was very limited, the search was subsequently expanded to include junctional and oesophageal cancer (OeC). Results A total of 28 articles (17 gastric cancer, 11 oesophageal cancer) met the inclusion criteria, analyzing 26,503 lymph nodes from 3711 GaC and 1912 OeC patients. The studies described eight different types of lymph node microarchitecture changes, categorized into three patterns: hyperplasia (SH, FH, PH), cell-specific infiltration (dendritic cells, T cells, neutrophils, macrophages), and differential gene expression. Meta-analysis of five GaC studies showed a positive association between SH in tumour-negative lymph nodes and better 5-year overall survival. Pooled risk ratios for all LNs showed increased 5-year overall survival for the presence of SH and PH. Conclusions This systematic review suggests that sinus histiocytosis and paracortical hyperplasia in regional tumour-negative lymph nodes may provide additional prognostic information for gastric and oesophageal cancer patients. Further studies are needed to better understand the lymph node reaction patterns and explore their impact of chemotherapy treatment and immunotherapy efficacy.

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The Prognostic Value of the Lymph Node in Oesophageal Adenocarcinoma; Incorporating Clinicopathological and Immunological Profiling

Cited by 6 publications

References 45 publications

Analysing the Combined Effects of Radiotherapy and Chemokine Receptor 5 Antagonism: Complementary Approaches to Promote T Cell Function and Migration in Oesophageal Adenocarcinoma

Analysing the Combined Effects of Radiotherapy and Chemokine Receptor 5 Antagonism: Complementary Approaches to Promote T Cell Function and Migration in Oesophageal Adenocarcinoma

Identification of plasma proteins associated with oesophageal cancer chemotherapeutic treatment outcomes using SWATH-MS

The clinical importance of the host anti-tumour reaction patterns in regional tumour draining lymph nodes in patients with locally advanced resectable gastric cancer: a systematic review and meta-analysis

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