Neoadjuvant immunotherapy in gastrointestinal cancers – The new standard of care?

Petričević, Branka; Kabiljo, Julijan; Zirnbauer, Rebecca; Walczak, Henning; Laengle, Johannes; Bergmann, Michael

doi:10.1016/j.semcancer.2022.05.015

Cited by 15 publications

(10 citation statements)

References 159 publications

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“…Chemotherapy and radiotherapy-induced immunogenic cell death may also help recruit intratumoural mature dendritic cells and activate cytotoxic T-cells. Both factors justify combining immunotherapy with standard neoadjuvant treatment to enhance antitumor response [7][8][9].…”

Section: Immune Checkpoint Inhibitors (Icis) Block the Inhibitory Sig...mentioning

confidence: 99%

“…A clinical trial in melanoma also demonstrates more significant tumour-resident T cell clone expansion with neoadjuvant compared to adjuvant immunotherapy [13]. Table 1 summarises the arguments for neoadjuvant and adjuvant immunotherapy [6,7,[12][13]14 && , [15][16][17][18]. In metastatic GI cancers, ICIs' effects are often considered suboptimal.…”

Section: Immune Checkpoint Inhibitors (Icis) Block the Inhibitory Sig...mentioning

confidence: 99%

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Immunotherapies in non-metastatic gastrointestinal cancers

Saúde-Conde¹,

Nguyen

Hendlisz

2023

Current Opinion in Oncology

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PurposeOver the last decade, immune checkpoint inhibitors (ICI) have emerged as cornerstone in the treatment of many metastatic tumour types, including gastrointestinal cancers. In many solid tumours, the effective therapies in the metastatic field are progressively brought into the curative setting. Consequently, earlier tumoural settings have become a field of experiment for immunotherapies. In melanoma, lung, and bladder cancers, excellent results were recorded, possibly explained by differences in the tumour microenvironment between metastatic and non-metastatic settings. In gastrointestinal (GI) Oncology, nivolumab is the first immune checkpoint inhibitor to become a standard-of-care adjuvant treatment after curative surgery for oesophagal or gastroesophageal junction cancer.Recent findingsWe herein discuss the results of a selection of the most relevant studies presented/published over the last 18 months testing immunotherapies in non-metastatic GI cancers. Among immunotherapies, ICI have been investigated in pre-, peri- and postoperative setting across tumour types, alone or in combination with chemo- and/or radiotherapy. Vaccines are also a new field of investigation.SummaryPromising results from two studies (NCT04165772 and NICHE-2 study) demonstrating never-seen-before responses to neoadjuvant immunotherapy in MMR deficient (dMMR) colorectal cancers raise hope for improving the patients’ outcome and developing organ-sparing strategies in this situation.

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Section: Immune Checkpoint Inhibitors (Icis) Block the Inhibitory Sig...mentioning

confidence: 99%

Section: Immune Checkpoint Inhibitors (Icis) Block the Inhibitory Sig...mentioning

confidence: 99%

Immunotherapies in non-metastatic gastrointestinal cancers

Saúde-Conde¹,

Nguyen

Hendlisz

2023

Current Opinion in Oncology

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“…Immune checkpoint inhibitors (ICIs) have emerged as a revolutionary approach to significantly improve cancer immunotherapy by targeting immune checkpoints. [ 1 ] Many studies have reported the safety and efficacy of immune checkpoint therapy in treating gastrointestinal tumors. [ 2 ] In the phase III KEYNOTE‐062 study, a monoclonal anti‐PD‐1 antibody showed single‐agent activity in patients with advanced gastric cancer (GC) with high microsatellite instability (MSI‐H).…”

Section: Introductionmentioning

confidence: 99%

Tumor Immunophenotyping‐Derived Signature Identifies Prognosis and Neoadjuvant Immunotherapeutic Responsiveness in Gastric Cancer

et al. 2023

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The effectiveness of neoadjuvant immune checkpoint inhibitor (ICI) therapy is confirmed in clinical trials; however, the patients suitable for receiving this therapy remain unspecified. Previous studies have demonstrated that the tumor microenvironment (TME) dominates immunotherapy; therefore, an effective TME classification strategy is required. In this study, five crucial immunophenotype-related molecules (WARS, UBE2L6, GZMB, BATF2, and LAG-3) in the TME are determined in five public gastric cancer (GC) datasets (n = 1426) and an in-house sequencing dataset (n = 79). Based on this, a GC immunophenotypic score (IPS) is constructed using the least absolute shrinkage and selection operator (LASSO) Cox, and randomSurvivalForest. IPS Low is characterized as immune-activated, and IPS High is immune-silenced. Data from seven centers (n = 1144) indicate that the IPS is a robust and independent biomarker for GC and superior to the AJCC stage. Furthermore, patients with an IPS Low and a combined positive score of ≥5 are likely to benefit from neoadjuvant anti-PD-1 therapy. In summary, the IPS can be a useful quantitative tool for immunophenotyping to improve clinical outcomes and provide a practical reference for implementing neoadjuvant ICI therapy for patients with GC.

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“…According to GLOBOCAN 2020, approximately 1,089,103 new cases and 768,793 deaths occur in 2020 and are associated with stomach cancer, making it the fifth most common cancer (excluding non-melanoma skin cancer) and the third most common cause of death by cancer among 36 cancer types, thus contributing to the high burden all around the world ( 8 ). With the advent of immune checkpoint blockades (ICBs), such as PD-1, PD-L1, and CTLA-4 monoclonal antibodies (mAbs), these offer novel treatment possibilities for solid cancer, with the crucial benefit of providing higher cure rates ( 9 ). Increasing evidence demonstrated that the application of ICBs is a new standard of targeted therapy in the treatment of stomach cancer and other kinds of cancers ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

Multi-omics profiling and digital image analysis reveal the potential prognostic and immunotherapeutic properties of CD93 in stomach adenocarcinoma

Guo

et al. 2023

Front. Immunol.

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BackgroundRecent evidence highlights the fact that immunotherapy has significantly improved patient outcomes. CD93, as a type I transmembrane glycoprotein, was correlated with tumor-associated angiogenesis; however, how CD93 correlates with immunotherapy in stomach adenocarcinoma (STAD) remains unclear.MethodsTCGA, GTEx, GEO, TIMER2.0, HPA, TISIDB, TCIA, cBioPortal, LinkedOmics, and ImmuCellAI public databases were used to elucidate CD93 in STAD. Visualization and statistical analysis of data were performed by R (Version 4.1.3), GraphPad (Version 8.0.1), and QuPath (Version 0.3.2).ResultsCD93 was highly expressed in STAD compared with adjacent normal tissues. The overexpression of CD93 was significantly correlated with a poor prognosis in STAD. There was a negative correlation between CD93 expression levels with CD93 mutation and methylation in STAD. Our results revealed that CD93 expression was positively associated with most immunosuppressive genes (including PD-1, PD-L1, CTLA-4, and LAG3), immunostimulatory genes, HLA, chemokine, and chemokine receptor proteins in STAD. Furthermore, in STAD, CD93 was noticeably associated with the abundance of multiple immune cell infiltration levels. Functional HALLMARK and KEGG term enhancement analysis of CD93 through Gene Set Enrichment Analysis was correlated with the process of the angiogenesis pathway. Subsequently, digital image analysis results by QuPath revealed that the properties of CD93+ cells were statistically significant in different regions of stomach cancer and normal stomach tissue. Finally, we utilized external databases, including GEO, TISIDB, ImmuCellAI, and TCIA, to validate that CD93 plays a key role in the immunotherapy of STAD.ConclusionOur study reveals that CD93 is a potential oncogene and is an indicative biomarker of a worse prognosis and exerts its immunomodulatory properties and potential possibilities for immunotherapy in STAD.

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Neoadjuvant immunotherapy in gastrointestinal cancers – The new standard of care?

Cited by 15 publications

References 159 publications

Immunotherapies in non-metastatic gastrointestinal cancers

Immunotherapies in non-metastatic gastrointestinal cancers

Tumor Immunophenotyping‐Derived Signature Identifies Prognosis and Neoadjuvant Immunotherapeutic Responsiveness in Gastric Cancer

Multi-omics profiling and digital image analysis reveal the potential prognostic and immunotherapeutic properties of CD93 in stomach adenocarcinoma

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