Tumor immune microenvironment is influenced by frameshift mutations and tumor mutational burden in gastric cancer

e21540 Background: This study aimed to investigate the immune microenvironment features and efficacy of PD-1/PD-L1 blockade of NSCLC with insertions in exon 20 (Ex20ins) of EGFR or HER2. Methods: Molecular spectrum, tumor mutational burden (TMB), PD-L1 protein expression, and the abundance of CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) were reviewed for NSCLC patients with Ex20ins of EGFR or HER2. Results: Thirty-five patients carrying EGFR Ex20ins and 21 patients harboring HER2 Ex20ins were retrospectively enrolled between April 2016 and September 2018. The average TMB was 3.3 mutations/megabase. PD-L1 expression in patients with EGFR Ex20ins was significantly higher than those with HER2 mutations (48.6% vs. 19.0%, P=0.027). High TMB and PD-L1 expression was independently associated with considerably poor prognosis (P=0.025, P=0.045; respectively). Finally, patients harboring EGFR Ex20ins seemed to be sensitive to PD-1/PD-L1 blockage whereas it showed limited efficacy in patients with HER2 Ex20ins. Conclusions: NSCLC patients with EGFR/ HER2 Ex20ins had distinct immune features. Patients with EGFR Ex20ins had significantly higher PD-L1 expression than those with HER2 mutations, which may be the underlying reason for the different responses to PD-1/PD-L1 blockage.

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Influence of Tumor Mutational Burden on Immune-infiltrating Cells in Stomach Adenocarcinoma

10.21203/rs.3.rs-122577/v1 ◽

2020 ◽

Author(s):

Zongxian Zhao ◽

Shilong Li ◽

Shuliang Li ◽

Huaxiang Yang ◽

Daohan Wang ◽

...

Keyword(s):

Gastric Cancer ◽

Receptor Interaction ◽

Nucleotide Polymorphisms ◽

Systematic Analysis ◽

Btb Domain ◽

Matrix Metalloproteinase 13 ◽

Mutational Burden ◽

Tumor Mutational Burden ◽

Stomach Adenocarcinoma ◽

N Stage

Abstract Background: Gastric cancer (GC) is one of the most common and fatal cancers worldwide. Tumor mutational burden (TMB) is described as a novel powerful signature to predict response to immunotherapy in gastric cancer. Nevertheless, tumor-infiltrating immune cells (TIICs) in different TMB GC remains unknown.Results: (1) The most common missense were single nucleotide polymorphisms and C>T. Furthermore, titin (TTN), tumor protein p53 (TP53), and mucin 16 (MUC16) had a higher rate of mutations in STAD. (2) TMB-high and -low groups were not associated with survival, T stage, M stage, and grade of patients with stomach adenocarcinoma (STAD) (Psurvival=0.086, PT=0.331, PM=0.804, Pgrade=0.695). However, TMB groupings were related with N stage and sex (PN=0.003, Psex=0.003). (3) There were intricate differences in immune infiltration cells (eg, T cells, monocytes, and mast cells) between the TMB-high and TMB-low groups. (4) A total of 458 genes were identified as DEGs; Dynein cytoplasmic 1 intermediate chain 1(DYNC1I1), matrix metalloproteinase 13 (MMP13) and zinc finger and BTB domain containing 16 (ZBTB16) were correlated with overall survival (OS). (5) DEGs were mainly involved in the regulation of the extracellular matrix-receptor interaction, and the Wnt and PI3K-AKT signaling pathways.Conclusion: The present study provides a comprehensive and systematic analysis of TMB and its clinical significance, and reveals the complicated differences of 22 TIICs between TMB-high and TMB-low groups in STAD.

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A PD-L1 Negative Advanced Gastric Cancer Patient With a Long Response to PD-1 Blockade After Failure of Systematic Treatment: A Case Report

Frontiers in Immunology ◽

10.3389/fimmu.2021.759250 ◽

2021 ◽

Vol 12 ◽

Author(s):

Fangyuan Zhang ◽

Jieying Zhang ◽

Lei Zhao ◽

Menglan Zhai ◽

Tao Zhang ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Patient ◽

Gastric Cancer Patient ◽

Immune Checkpoint ◽

Immune Checkpoint Blockade ◽

Checkpoint Blockade ◽

Systematic Treatment ◽

Mutational Burden ◽

Tumor Mutational Burden ◽

Gastric Cancer Patients

BackgroundIt was widely accepted that programmed death-ligand 1 (PD-L1) positive, tumor mutational burden-high (TMB-H) or microsatellite instability-high (MSI-H) tumor are prone to have better treatment response to immune checkpoint blockade. The value of immune checkpoint blockade in PD-L1 negative gastric cancer patients has been questioned due to lower objective response rate (ORR).Case PresentationWe report an unusual case of a PD-L1 negative, proficient mismatch repair (pMMR)/microsatellite stability (MSS), tumor mutational burden-low (TMB-L) gastric cancer patient who achieved good response to immune checkpoint blockade after failure of systematic treatment. Multiple lymph nodes and bone metastases are the main characteristics of this patient. The patient survived for more than 30 months after diagnosis.ConclusionsThis case suggested that PD-L1 negative gastric cancer patient may also benefit from immune checkpoint blockade. In gastric cancer, patients with lymph node metastasis may be potential beneficiaries.

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