Clinical Application of Adaptive Immune Therapy in MSS Colorectal Cancer Patients

Wang, Danyang; Zhang, Hangyu; Tao, Xiang; Wang, Gang

doi:10.3389/fimmu.2021.762341

Cited by 17 publications

(13 citation statements)

References 68 publications

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“…However, dMMR/MSI-H CRC comprises approximately 5% of metastatic CRC, and the efficacy of ICIs has been unsatisfactory in the majority of CRC which is mismatch repair proficient (pMMR) or microsatellite stable (MSS) [ 66 , 67 ]. Because MSS metastatic CRC is usually classified as a typical “cold” cancer that presents a lack of the activation of immune responses, the studies investigating how to generate a “hot” TME are critical to the treatment improvement of MSS CRC [ 68 , 69 ]. The production of CXCL9 in the TME can induce T-cell infiltration and may contribute to the orchestration of the “hot” TME of MSS CRC.…”

Section: Discussionmentioning

confidence: 99%

PD-L1 Expression in High-Risk Early-Stage Colorectal Cancer—Its Clinical and Biological Significance in Immune Microenvironment

Chung

Liao

Lin

et al. 2022

IJMS

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Programmed death-ligand 1 (PD-L1) is an immune checkpoint molecule that can regulate immune responses in the tumor microenvironment (TME); however, the clinical applications of PD-L1 in early-stage colorectal cancer (CRC) remain unclear. In this study, we aimed to investigate the relationship between PD-L1 expression and survival outcome and explore its relevant immune responses in CRC. PD-L1 expression was evaluated by immunohistochemical staining to determine the tumor proportion score and combined positive score (CPS) in a Taiwanese CRC cohort. The oncomine immune response research assay was conducted for immune gene expression analyses. CRC datasets from the TCGA database were reappraised for PD-L1-associated gene enrichment analyses using GSEA. The high expression of PD-L1 (CPS ≥ 5) was associated with longer recurrence-free survival (p = 0.031) and was an independent prognostic factor as revealed by multivariate analysis. High PD-L1 expression was related to six immune-related gene signatures, and CXCL9 is the most significant overexpressed gene in differential analyses. High CXCL9 expression correlated with increased infiltration levels of immune cells in the TME, including CD8+ T lymphocytes and M1 macrophages. These findings suggest that high PD-L1 expression is a prognostic factor of early-stage CRC, and CXCL9 may play a key role in regulating PD-L1 expression.

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Section: Discussionmentioning

confidence: 99%

PD-L1 Expression in High-Risk Early-Stage Colorectal Cancer—Its Clinical and Biological Significance in Immune Microenvironment

Chung

Liao

Lin

et al. 2022

IJMS

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“…Nowadays, the principle of most therapeutic cancer vaccine is based on the establishment of TAA -specific antitumor immune response to eliminate tumor cells expressing these antigens ( 91 ). Cancer vaccines include cell (autologous, DC) vaccines, protein/peptide vaccines, and gene vaccines ( 92 ) ( Figure 1 ). Many studies have identified a variety of TAA expressed by CRC cells as potential targets for vaccine immunotherapy, including CEA, WT1, MUC1, RNF43, GUCY2C, SART3, and hTERT ( 91 ).…”

Section: Cancer Vaccinesmentioning

confidence: 99%

Immunotherapies catering to the unmet medical need of cold colorectal cancer

Yuan

Gao

et al. 2022

Front. Immunol.

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As a common malignant tumor of gastrointestinal tract, the incidence of colorectal cancer (CRC) has gradually increased in recent years. In western developed countries, it has even become the second largest malignant tumor next to lung cancer. Immunotherapy is a hot topic in the field of cancer therapy, including immune checkpoint blockade (ICB), adoptive cell therapy (ACT), cancer vaccines and cytokines, aiming to improve the ability of the immune system to recognize, target and eliminate cancer cells. However, cold CRC, which accounts for a high proportion of CRC, is not so reactive to it. The development of immunotherapy to prevent cancer cells from forming “immune escape” pathways to the immune system in cold CRC, has been under increasing study attention. There is proof that an organic combination of radiotherapy, chemotherapy, and several immunotherapies can considerably boost the immune system’s capacity to eradicate tumor cells. In this review, we summarized the role of immunotherapy in colorectal cancer. In addition, we propose a breakthrough and strategy to improve the role of immunotherapy in cold CRC based on its characteristics.

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“…For precise tumor targeting, potential solutions can be used, such as targeting T-cells with tandem CARs, universal CARs, affinity tuning, and regulation of CAR expression levels ( 166 ). In addition, preliminary data have provided promising evidence for combination therapies of CAR T-cells and other immunotherapies, chemotherapy, or radiotherapy ( 167 ).…”

Section: Car T-cell Trials In Crcmentioning

confidence: 99%

CAR T-cells for colorectal cancer immunotherapy: Ready to go?

et al. 2022

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Chimeric antigen receptor (CAR) T-cells represent a new genetically engineered cell-based immunotherapy tool against cancer. The use of CAR T-cells has revolutionized the therapeutic approach for hematological malignancies. Unfortunately, there is a long way to go before this treatment can be developed for solid tumors, including colorectal cancer. CAR T-cell therapy for colorectal cancer is still in its early stages, and clinical data are scarce. Major limitations of this therapy include high toxicity, relapses, and an impermeable tumor microenvironment for CAR T-cell therapy in colorectal cancer. In this review, we summarize current knowledge, highlight challenges, and discuss perspectives regarding CAR T-cell therapy in colorectal cancer.

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Clinical Application of Adaptive Immune Therapy in MSS Colorectal Cancer Patients

Cited by 17 publications

References 68 publications

PD-L1 Expression in High-Risk Early-Stage Colorectal Cancer—Its Clinical and Biological Significance in Immune Microenvironment

PD-L1 Expression in High-Risk Early-Stage Colorectal Cancer—Its Clinical and Biological Significance in Immune Microenvironment

Immunotherapies catering to the unmet medical need of cold colorectal cancer

CAR T-cells for colorectal cancer immunotherapy: Ready to go?

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