Two distinct phenotypes of immunologically hot gastric cancer subtypes

Saito, Noriyuki; Kobayashi, Yukari; Nagaoka, Koji; Kushihara, Yoshihiro; Sato, Yasuyoshi; Wada, Ikuo; Kakimi, Kazuhiro; Seto, Yasuyuki

doi:10.1016/j.bbrep.2021.101167

Cited by 2 publications

(3 citation statements)

References 21 publications

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“…Other authors tried to characterize TME in GC, on the basis of chromatin accessibility [38], DE of genes associated with cell adhesion and metabolism [39], TME cell infiltration subtypes [16], or signatures of immune-genomic profiling [40]. Our data are in line with literature and underline the need to further increase the knowledge of TME in GC, with particular focus on how TME is affected by CT.…”

Section: Discussionsupporting

confidence: 84%

Dynamic Profiling of the Immune Tumor Microenvironment in Locally Advanced Gastric Cancer Treated with Perioperative Chemotherapy

Pecora¹,

Ugolini²,

Giannini³

et al. 2023

Oncology

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Introduction: In locally advanced gastric cancer (GC), FLOT represents the standard perioperative regimen and combination with immunotherapy is under investigation. However, the role of immune tumor microenvironment (TME) is poorly recognized in this setting. We aimed to study TME characteristics and dynamics during FLOT. Methods: Paired biopsy (PRE) and surgical (POST) samples of 25 patients treated with FLOT were prospectively analyzed. After collection of clinic-pathological data, NanoString analyses were performed. The primary objective of the study was to assess the changes induced by chemotherapy in POST compared to PRE samples. Results: The unsupervised hierarchical method analysis clearly distinguished PRE and POST samples, even though some cases showed high immune gene expression at baseline. When POST samples were compared with PRE, a differential expression in hyper-expressed gene sets related to cytotoxicity, T-cell functions, complement system, tumor necrosis factor superfamily, cell cycle, and regulation was recognized. Downstaging of the primary tumor (T-regression, measured by pathologic compared to clinical T stage) was the covariate most frequently associated with these changes. Using the immune cell profiling, cases with T-regression reported a significant increase of T, CD8+ T and B cells and a decrease in mast cells, while nonresponders demonstrated an increase of T, B, cytotoxic, and mast cells. Conclusion: Our analysis shows that FLOT significantly influences immune TME of GC. While relevant modifications preferentially occur in tumors showing primary tumor regression, response to treatment seems to be associated with a specific immune profile.

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Section: Discussionsupporting

confidence: 84%

Dynamic Profiling of the Immune Tumor Microenvironment in Locally Advanced Gastric Cancer Treated with Perioperative Chemotherapy

Pecora¹,

Ugolini²,

Giannini³

et al. 2023

Oncology

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“…Moreover, metabolic and cell adhesion pathways were distinct between Hot 1 and Hot 2 malignancies. 41 Hence, it is imperative to incorporate active metabolism modulation into treatment strategies for Hot 1 tumors. While these immunological subtypes and TCGA molecular subtypes shared some degree of overlap, histological or molecular…”

Section: Gastric Cancer Is Classified Immunologically Using An Immuno...mentioning

confidence: 99%

“…Survival was superior in Hot2 subtypes in their cohort as well as TCGA cohort. Moreover, metabolic and cell adhesion pathways were distinct between Hot 1 and Hot 2 malignancies 41 . Hence, it is imperative to incorporate active metabolism modulation into treatment strategies for Hot 1 tumors.…”

Section: Unique Landscapes Of Immunotherapeutic Strategiesmentioning

confidence: 99%

Microsatellite instability: A 2024 update

Yamamoto,

Watanabe,

Arai

et al. 2024

Cancer Science

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Deficient mismatch repair (dMMR) results in microsatellite instability (MSI), a pronounced mutator phenotype. High‐frequency MSI (MSI‐H)/dMMR is gaining increasing interest as a biomarker for advanced cancer patients to determine their eligibility for immune checkpoint inhibitors (ICIs). Various methods based on next‐generation sequencing (NGS) have been developed to assess the MSI status. Comprehensive genomic profiling (CGP) testing can precisely ascertain the MSI status as well as genomic alterations in a single NGS test. The MSI status can be also ascertained through the liquid biopsy‐based CGP assays. MSI‐H has thus been identified in various classes of tumors, resulting in a greater adoption of immunotherapy, which is hypothesized to be effective against malignancies that possess a substantial number of mutations and/or neoantigens. NGS‐based studies have also characterized MSI‐driven carcinogenesis, including significant rates of fusion kinases in colorectal cancers (CRCs) with MSI‐H that are targets for therapeutic kinase inhibitors, particularly in MLH1‐methylated CRCs with wild‐type KRAS/BRAF. NTRK fusion is linked to the colorectal serrated neoplasia pathway. Recent advances in investigations of MSI‐H malignancies have resulted in the development of novel diagnostic or therapeutic techniques, such as a synthetic lethal therapy that targets the Werner gene. DNA sensing in cancer cells is required for antitumor immunity induced by dMMR, opening up novel avenues and biomarkers for immunotherapy. Therefore, clinical relevance exists for analyses of MSI and MSI‐H‐associated genomic alterations in malignancy. In this article, we provide an update on MSI‐driven carcinogenesis, with an emphasis on unique landscapes of diagnostic and immunotherapeutic strategies.

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Two distinct phenotypes of immunologically hot gastric cancer subtypes

Cited by 2 publications

References 21 publications

Dynamic Profiling of the Immune Tumor Microenvironment in Locally Advanced Gastric Cancer Treated with Perioperative Chemotherapy

Dynamic Profiling of the Immune Tumor Microenvironment in Locally Advanced Gastric Cancer Treated with Perioperative Chemotherapy

Microsatellite instability: A 2024 update

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