Current progress and future perspectives of neoadjuvant anti-PD-1/PD-L1 therapy for colorectal cancer

Yang, Zhengyang; Wu, Guang; Zhang, Xiao; Gao, Jiale; Ma, Cong; Wei, Qi; Sun, Liting; Wei, Pengyu; Bai, Zhigang; Yao, Hongwei; Zhang, Zhongtao

doi:10.3389/fimmu.2022.1001444

Cited by 31 publications

(19 citation statements)

References 93 publications

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“…Specifically, the use of immune checkpoint inhibitors (ICIs), such as CTLA4, PD-1, PD-L1, MSI-H, or dMMR, received much attention. These markers can predict the response to immunotherapy in CRC treatment ( 44 – 46 ). Furthermore, drug sensitivity analysis revealed that the low-risk group displayed increased susceptibility to oxaliplatin and dabrafenib.…”

Section: Discussionmentioning

confidence: 99%

Development of an anoikis-related gene signature and prognostic model for predicting the tumor microenvironment and response to immunotherapy in colorectal cancer

Li,

Weng,

Yang

et al. 2024

Front. Immunol.

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The effect of anoikis-related genes (ARGs) on clinicopathological characteristics and tumor microenvironment remains unclear. We comprehensively analyzed anoikis-associated gene signatures of 1057 colorectal cancer (CRC) samples based on 18 ARGs. Anoikis-related molecular subtypes and gene features were identified through consensus clustering analysis. The biological functions and immune cell infiltration were assessed using the GSVA and ssGSEA algorithms. Prognostic risk score was constructed using multivariate Cox regression analysis. The immunological features of high-risk and low-risk groups were compared. Finally, DAPK2-overexpressing plasmid was transfected to measure its effect on tumor proliferation and metastasis in vitro and in vivo. We identified 18 prognostic ARGs. Three different subtypes of anoikis were identified and demonstrated to be linked to distinct biological processes and prognosis. Then, a risk score model was constructed and identified as an independent prognostic factor. Compared to the high-risk group, patients in the low-risk group exhibited longer survival, higher enrichment of checkpoint function, increased expression of CTLA4 and PD-L1, higher IPS scores, and a higher proportion of MSI-H. The results of RT-PCR indicated that the expression of DAPK2 mRNA was significantly downregulated in CRC tissues compared to normal tissues. Increased DAPK2 expression significantly suppressed cell proliferation, promoted apoptosis, and inhibited migration and invasion. The nude mice xenograft tumor model confirmed that high expression of DAPK2 inhibited tumor growth. Collectively, we discovered an innovative anoikis-related gene signature associated with prognosis and TME. Besides, our study indicated that DAPK2 can serve as a promising therapeutic target for inhibiting the growth and metastasis of CRC.

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Section: Discussionmentioning

confidence: 99%

Development of an anoikis-related gene signature and prognostic model for predicting the tumor microenvironment and response to immunotherapy in colorectal cancer

Li,

Weng,

Yang

et al. 2024

Front. Immunol.

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“…5 ). Additionally, immune checkpoint inhibitors (ICIs) effective for CRC patients when the genetic phenotypes are mismatch-repair-deficient or microsatellite instability-high (dMMR/MSI-H) [ 29 ]. Recent studies have shown that PPARG induces programmed cell death ligand 1 (PD-L1) expression in CRC [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

SLC27A2 mediates FAO in colorectal cancer through nongenic crosstalk regulation of the PPARs pathway

Shang

Che

et al. 2023

BMC Cancer

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Background Peroxisome proliferator activated receptors (PPARs) are a nuclear hormone receptors superfamily that is closely related to fatty acid (FA) metabolism and tumor progression. Solute carrier family 27 member 2 (SLC27A2) is important for FA transportation and metabolism and is related to cancer progression. This study aims to explore the mechanisms of how PPARs and SLC27A2 regulate FA metabolism in colorectal cancer (CRC) and find new strategies for CRC treatment. Methods Biological information analysis was applied to detect the expression and the correlation of PPARs and SLC27A2 in CRC. The protein–protein interaction (PPI) interaction networks were explored by using the STRING database. Uptake experiments and immunofluorescence staining were used to analyse the function and number of peroxisomes and colocalization of FA with peroxisomes, respectively. Western blotting and qRT‒PCR were performed to explore the mechanisms. Results SLC27A2 was overexpressed in CRC. PPARs had different expression levels, and PPARG was significantly highly expressed in CRC. SLC27A2 was correlated with PPARs in CRC. Both SLC27A2 and PPARs were closely related to fatty acid oxidation (FAO)‒related genes. SLC27A2 affected the activity of ATP Binding Cassette Subfamily D Member 3 (ABCD3), also named PMP70, the most abundant peroxisomal membrane protein. We found that the ratios of p-Erk/Erk and p-GSK3β/GSK3β were elevated through nongenic crosstalk regulation of the PPARs pathway. Conclusions SLC27A2 mediates FA uptake and beta-oxidation through nongenic crosstalk regulation of the PPARs pathway in CRC. Targeting SLC27A2/FATP2 or PPARs may provide new insights for antitumour strategies.

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“…PD-1/PD-L1 inhibitors are currently the most focused immunotherapies and have achieved brilliant results in various tumor types ( 8 , 82 ). Intratumoral injections can likewise reduce systemic immune adverse effects while ensuring better efficacy.…”

Section: Intratumoral Ablative Agents and Immunotherapy Drugsmentioning

confidence: 99%

Chemo-immunoablation of solid tumors: A new concept in tumor ablation

2023

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Chemical ablation was designed to inject chemical agents directly into solid tumors to kill cells and is currently only used clinically for the palliative treatment of tumors. The application and combination of different drugs, from anhydrous ethanol, and glacial acetic acid to epi-amycin, have been clinically tested for a long time. The effectiveness is unsatisfactory due to chemical agents’ poor diffusion and concentration. Immunotherapy is considered a prospective oncologic therapeutic. Still, the clinical applications were limited by the low response rate of patients to immune drugs and the immune-related adverse effects caused by high doses. The advent of intratumoral immunotherapy has well addressed these issues. However, the efficacy of intratumoral immunotherapy alone is uncertain, as suggested by the results of preclinical and clinical studies. In this study, we will focus on the research of immunosuppressive tumor microenvironment with chemoablation and intratumoral immunotherapy, the synergistic effect between chemotherapeutic drugs and immunotherapy. We propose a new concept of intratumoral chemo-immunoablation. The concept opens a new perspective for tumor treatment from direct killing of tumor cells while, enhancing systemic anti-tumor immune response, and significantly reducing adverse effects of drugs.

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Current progress and future perspectives of neoadjuvant anti-PD-1/PD-L1 therapy for colorectal cancer

Cited by 31 publications

References 93 publications

Development of an anoikis-related gene signature and prognostic model for predicting the tumor microenvironment and response to immunotherapy in colorectal cancer

Development of an anoikis-related gene signature and prognostic model for predicting the tumor microenvironment and response to immunotherapy in colorectal cancer

SLC27A2 mediates FAO in colorectal cancer through nongenic crosstalk regulation of the PPARs pathway

Chemo-immunoablation of solid tumors: A new concept in tumor ablation

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