Human Leukocyte Antigen Class I Deficiency in Gastric Carcinoma

Iwasaki, Akiko; Shinozaki‐Ushiku, Aya; Kunita, Akiko; Yamazawa, Sho; Sato, Yasuyoshi; Yamashita, Hiroharu; Fukayama, Masashi; Seto, Yasuyuki; Ushiku, Tetsuo

doi:10.1097/pas.0000000000001779

Cited by 10 publications

(5 citation statements)

References 33 publications

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“…The results showed that the frequency of HLA-I defects (≥1%) in MSI tumors was obviously higher (52%) than that in EBVpositive tumors (23%) and other tumors (28%). Additionally, HLA-I-deficient tumor areas had a significant lower levels of CD8 (+) cells infiltration than HLA-I-preserved tumor areas within the tumor (Iwasaki et al, 2021). I believe that these experimental results will leave adequate room for imagination about the effect of tumor antigen alteration and its presentation on ICIs.…”

Section: Deficiency Of Tumor Antigen Presentationmentioning

confidence: 87%

Resistance to immune checkpoint inhibitors in gastric cancer

Liu,

Yuan,

Wang

et al. 2023

Front. Pharmacol.

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Gastric cancer (GC) is one of the most common gastrointestinal malignancies worldwide. In the past decade, with the development of early diagnostic techniques, a clear decline in GC incidence has been observed, but its mortality remains high. The emergence of new immunotherapies such as immune checkpoint inhibitors (ICIs) has changed the treatment of GC patients to some extent. However, only a small number of patients with advanced GC have a durable response to ICI treatment, and the efficacy of ICIs is very limited. Existing studies have shown that the failure of immunotherapy is mainly related to the development of ICI resistance in patients, but the understanding of the resistance mechanism is still insufficient. Therefore, clarifying the mechanism of GC immune resistance is critical to improve its treatment and clinical benefit. In this review, we focus on summarizing the mechanisms of primary or acquired resistance to ICI immunotherapy in GC from both internal and external aspects of the tumor. At the same time, we also briefly discuss some other possible resistance mechanisms in light of current studies.

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Section: Deficiency Of Tumor Antigen Presentationmentioning

confidence: 87%

Resistance to immune checkpoint inhibitors in gastric cancer

Liu,

Yuan,

Wang

et al. 2023

Front. Pharmacol.

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“…Interestingly, the frequency of HLA class I downregulation in Epstein-Barr virus (EBV)-related gastric cancer, for which ICIs are also effective due to its high antigenicity, is similar to that in non-MSI and non-EBV-related gastric cancer. 118 This is assumed because, in EBV-related gastric cancer, genetic mutations do not occur to the same extent as in dMMR/MSI cancer. Interestingly, unlike colorectal or gastric cancer, there is no comparable pattern observed between dMMR and expression of HLA class I in endometrial cancer.…”

Section: Significance Of Evaluating Hla Class I Molecules Expressed I...mentioning

confidence: 99%

“…In other words, the propensity for acquiring genetic mutations is thought to result in high antigenicity, while also leading to the loss of HLA class I expression. Interestingly, the frequency of HLA class I downregulation in Epstein–Barr virus (EBV)‐related gastric cancer, for which ICIs are also effective due to its high antigenicity, is similar to that in non‐MSI and non‐EBV‐related gastric cancer 118 . This is assumed because, in EBV‐related gastric cancer, genetic mutations do not occur to the same extent as in dMMR/MSI cancer.…”

Section: Significance Of Evaluating Hla Class I Molecules Expressed I...unclassified

Assessment of cancer cell‐expressed HLA class I molecules and their immunopathological implications

Kubo,

Asano,

Sasaki

et al. 2024

HLA

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Immunotherapy using immune checkpoint inhibitors (ICIs) has shown superior efficacy compared with conventional chemotherapy in certain cancer types, establishing immunotherapy as the fourth standard treatment alongside surgical intervention, chemotherapy, and radiotherapy. In cancer immunotherapy employing ICIs, CD8‐positive cytotoxic T lymphocytes are recognized as the primary effector cells. For effective clinical outcomes, it is essential that the targeted cancer cells express HLA class I molecules to present antigenic peptides derived from the tumor. However, cancer cells utilize various mechanisms to downregulate or lose HLA class I molecules from their surface, resulting in evasion from immune surveillance. Correlations between prognosis and the integrity of HLA class I molecules expressed by cancer cells have been consistently found across different types of cancer. This paper provides an overview of the regulatory mechanisms of HLA class I molecules and their role in cancer immunotherapy, with a particular emphasis on the significance of utilizing pathological tissues to evaluate HLA class I molecules expressed in cancer cells.

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“…The degree of CD8+ T-cell infiltration is significantly reduced in HLA-I-deficient tumor areas. Therefore, HLA-I and PD-L1 should be considered a common mechanism of immune escape, especially in the MSI subtype, which could become a biomarker predicting response to immune checkpoint inhibitor therapy in gastric cancer [203]. The frequency of loss of HLA heterozygosity among advanced solid tumor colorectal cancers is between 13.5-23%, which is consistent with that in primary tumors from TCGA, with no association with clinical biomarkers (KRAS, BRAF, and MSI status) [204].…”

Section: Microbiome and Major Histocompatibility Complex (Mhc) Crosstalkmentioning

confidence: 99%

Host Transcriptional Regulatory Genes and Microbiome Networks Crosstalk through Immune Receptors Establishing Normal and Tumor Multiomics Metafirm of the Oral-Gut-Lung Axis

Otálora-Otálora,

López-Rivera,

Aristizábal-Guzmán

et al. 2023

IJMS

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The microbiome has shown a correlation with the diet and lifestyle of each population in health and disease, the ability to communicate at the cellular level with the host through innate and adaptative immune receptors, and therefore an important role in modulating inflammatory process related to the establishment and progression of cancer. The oral cavity is one of the most important interaction windows between the human body and the environment, allowing the entry of an important number of microorganisms and their passage across the gastrointestinal tract and lungs. In this review, the contribution of the microbiome network to the establishment of systemic diseases like cancer is analyzed through their synergistic interactions and bidirectional crosstalk in the oral-gut-lung axis as well as its communication with the host cells. Moreover, the impact of the characteristic microbiota of each population in the formation of the multiomics molecular metafirm of the oral-gut-lung axis is also analyzed through state-of-the-art sequencing techniques, which allow a global study of the molecular processes involved of the flow of the microbiota environmental signals through cancer-related cells and its relationship with the establishment of the transcription factor network responsible for the control of regulatory processes involved with tumorigenesis.

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Human Leukocyte Antigen Class I Deficiency in Gastric Carcinoma

Cited by 10 publications

References 33 publications

Resistance to immune checkpoint inhibitors in gastric cancer

Resistance to immune checkpoint inhibitors in gastric cancer

Assessment of cancer cell‐expressed HLA class I molecules and their immunopathological implications

Host Transcriptional Regulatory Genes and Microbiome Networks Crosstalk through Immune Receptors Establishing Normal and Tumor Multiomics Metafirm of the Oral-Gut-Lung Axis

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