2020
DOI: 10.21037/tgh.2019.12.11
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Finding the hot spot: identifying immune sensitive gastrointestinal tumors

Abstract: Although researchers have been trying to harness the immune system for over 100 years, the advent of immune checkpoint blockers (ICB) marks an era of significant clinical outcomes in various metastatic solid tumors, characterized by complete and durable responses. ICBs are monoclonal antibodies that target either of a pair of transmembrane molecules in tumors or T-cells involved in immune evasion.Currently 2 ICBs targeting the checkpoint program death 1 (PD-1), nivolumab and pembrolizumab, and one cytotoxic ly… Show more

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Cited by 7 publications
(5 citation statements)
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“…Nivolumab is a commonly used immune checkpoint inhibitor in Japan (1). It is thought to be highly effective in patients with tumors highly expressing PD-L1 or including high immunogenicity, the so called 'hot tumor' (13). We refer to PD-L1 expression as an e cacy indicator of ICIs in various types of tumors (3,(14)(15)(16)(17).…”
Section: Discussionmentioning
confidence: 99%
“…Nivolumab is a commonly used immune checkpoint inhibitor in Japan (1). It is thought to be highly effective in patients with tumors highly expressing PD-L1 or including high immunogenicity, the so called 'hot tumor' (13). We refer to PD-L1 expression as an e cacy indicator of ICIs in various types of tumors (3,(14)(15)(16)(17).…”
Section: Discussionmentioning
confidence: 99%
“…通过Lokuhetty等人 [9] 提出的模型及其他相关工作 的发表, 结直肠癌发生相关的主要基因改变已基本清 [36] . 已有报道, POLE/POLD1突变的病例, 女性、左半结肠多见, 80% 为单纯腺癌, 14%伴有黏液特征 [37,38] . 但总体病例少, 还 未明确该组病例的特征.…”
Section: Who对于结直肠癌分类的内容基本稳定unclassified
“…Dysfunctional T helper 1 (Th1) cells and reduced cytokine expression [189,190] Reduced expression of absent in melanoma 2 (AIM2) Decreases inflammation [181] Reduced expression of poliovirus receptor-related immunoglobulin domain containing protein (PVRIG) Dysfunctional CD8 + T cells [181] Increased expression of mannosidase alpha class 2A member 1 (MAN2A1) Altered Th1/T-helper 2 (Th2) axis towards Th2 expression [181] Another cause of resistance to anti-PD-L1 immune checkpoint inhibitors is a reduction in neoantigen expression on the tumour cell surface. A lack of neoantigens, either due to a low tumour mutational burden, or altered antigen processing and presentation, results in a reduced immune response to the tumour, which compensates for the immunosuppressive effects of PD-L1 signalling that have been lost [180,185,191].…”
Section: Event Impact On the Tumour Microenvironmentmentioning
confidence: 99%
“…Resistance to anti-PD-L1 immune checkpoint inhibitors will eventually occur in the majority of patients, although there are differences in rates between tumour types. This can be a consequence of PD-L1 upregulation [ 175 , 176 , 177 ], which can occur due to increased JAK-STAT signalling, caused by: loss of the tumour suppressor FBP1 [ 176 , 178 ], mutations in JAK1/2 [ 179 ], or stimulation of tumour cells’ interferon-gamma receptor 2 by interferon-gamma released from activated CD8 + T cells in the tumour microenvironment [ 180 , 181 ]. PD-L1 upregulation can also occur when loss of the tumour suppressor PTEN results in increased PI3K/Akt signalling [ 176 , 177 ].…”
Section: Mechanisms Of Resistance To Alcl Therapymentioning
confidence: 99%
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