Academic Journal
Immuno-Contexture and Immune Checkpoint Molecule Expression in Mismatch Repair Proficient Colorectal Carcinoma
| العنوان: | Immuno-Contexture and Immune Checkpoint Molecule Expression in Mismatch Repair Proficient Colorectal Carcinoma |
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| المؤلفون: | Giacomelli, Mauro, Monti, Matilde, Pezzola, Diego Cesare, Lonardi, Silvia, Bugatti, Mattia, Missale, Francesco, Cioncada, Rossella, Melocchi, Laura, Giustini, Viviana, Villanacci, Vincenzo, Baronchelli, Carla, Manenti, Stefania, Imberti, Luisa, Giurisato, Emanuele, Vermi, William |
| المساهمون: | Giacomelli Mauro, Monti Matilde, Pezzola Diego Cesare, Lonardi Silvia, Bugatti Mattia, Missale Francesco, Cioncada Rossella, Melocchi Laura, Giustini Viviana, Villanacci Vincenzo, Baronchelli Carla, Manenti Stefania, Imberti Luisa, Giurisato Emanuele, Vermi William |
| سنة النشر: | 2023 |
| المجموعة: | Università degli Studi di Brescia: OPENBS - Open Archive UniBS |
| مصطلحات موضوعية: | PD-L1, T-cell exhaustion, colorectal cancer, double negative T cell, immune checkpoint, interferon-γ, microsatellite instability, mismatch repair, tumor microenvironment |
| الوصف: | Simple SummaryConsensus Molecular Subtypes have recently been proposed based on molecular and immune landscape of colorectal carcinoma (CRC). Only mismatch repair deficient and hyper-mutated CRC (CRCdMMR) can obtain clinical benefits from immune checkpoint blockades; on the other hand, mismatch repair proficient CRCs (CRCpMMR) have very limited therapeutic options. This study establishes that CRCpMMR displays an immunosuppressive microenvironment containing abundant tumor-associated macrophages (TAMs) and neutrophils, with a reduction in double negative T lymphocytes and B cells and increased exhausted tumor-infiltrating lymphocytes. Poor immunogenicity in CRCpMMR is further supported by interferon gamma (IFN-?) unresponsiveness of both tumor cells and TAMs.Colorectal carcinoma (CRC) represents a lethal disease with heterogeneous outcomes. Only patients with mismatch repair (MMR) deficient CRC showing microsatellite instability and hyper-mutated tumors can obtain clinical benefits from current immune checkpoint blockades; on the other hand, immune- or target-based therapeutic strategies are very limited for subjects with mismatch repair proficient CRC (CRCpMMR). Here, we report a comprehensive typing of immune infiltrating cells in CRCpMMR. We also tested the expression and interferon-?-modulation of PD-L1/CD274. Relevant findings were subsequently validated by immunohistochemistry on fixed materials. CRCpMMR contain a significantly increased fraction of CD163(+) macrophages (TAMs) expressing TREM2 and CD66(+) neutrophils (TANs) together with decrease in CD4(-)CD8(-)CD3(+) double negative T lymphocytes (DNTs); no differences were revealed by the analysis of conventional and plasmacytoid dendritic cell populations. A fraction of tumor-infiltrating T-cells displays an exhausted phenotype, co-expressing PD-1 and TIM-3. Remarkably, expression of PD-L1 on fresh tumor cells and TAMs was undetectable even after in vitro stimulation with interferon-?. These findings confirm the immune suppressive microenvironment of ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/37370706; info:eu-repo/semantics/altIdentifier/wos/WOS:001020681900001; volume:15; issue:12; journal:CANCERS; https://hdl.handle.net/11379/596921; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85163813434 |
| DOI: | 10.3390/cancers15123097 |
| الاتاحة: | https://hdl.handle.net/11379/596921 https://doi.org/10.3390/cancers15123097 |
| رقم الانضمام: | edsbas.5296C5A4 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/cancers15123097 |
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