Tumor-Infiltrating Lymphocytes in Colorectal Cancer: The Fundamental Indication and Application on Immunotherapy

Bai, Ziyi; Zhou, Yao; Ye, Zifan; Xiong, Jialong; Lan, Hongying; Wang, Feng

doi:10.3389/fimmu.2021.808964

Cited by 64 publications

(48 citation statements)

References 155 publications

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“…Based on such immune cell infiltration and their activation status, the low-risk samples could be assigned to inflamed tumors (Nishikawa and Koyama, 2021). According to previous research, this kind of tumor immune microenvironment would have a stronger response to immunotherapy (Bai et al, 2021).…”

Section: Discussionmentioning

confidence: 92%

Amino acid metabolism genes associated with immunotherapy responses and clinical prognosis of colorectal cancer

Peng

Zheng

Guo

et al. 2022

Front. Mol. Biosci.

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Based on amino acid metabolism-related genes (AAMRGs), this study aimed at screening out key prognosis-related genes and finding the underlying correlation between the amino acid metabolism and tumor immune microenvironment of colorectal cancer. A total of 448 amino acid metabolism-related genes were obtained from MsigDB. The risk signature was built based on differential expression genes, univariate Cox, and LASSO analyses with 403 patients’ data downloaded from the TCGA database. Survival analysis and independence tests were performed to confirm the validity of the risk signature. Single-sample gene set enrichment analysis (ssGSEA), tumor mutation burden (TMB), the score of tumor immune dysfunction and exclusion (TIDE), the immunophenoscore obtained from The Cancer Immunome Atlas database, and the IC50 of drugs were used to find the relationship among the risk signature, immune status, immunotherapy response, and drug sensitivity of colorectal cancer. We identified five amino acid metabolism-related genes for the construction of the risk signature, including ENOPH1, ACAT1, ALDH4A1, FAS, and ASPG. The low-risk group was significantly associated with a better prognosis (p < 0.0001). In the entire set, the area under the curve (AUC) for 1, 3, and 5 years was 0.717, 0.734, and 0.764, respectively. We also discovered that the low-risk subgroup was related to more activity of immune cells, had higher expression of some immune checkpoints, and was more likely to benefit from immunotherapy. ssGSEA revealed that except the processes of glutamine histidine, lysine, tyrosine, and L-phenylalanine metabolism, the other amino acid metabolism pathways were more active in the samples with the low risk scores, whereas the activities of synthesis and transportation of most amino acids were similar. Hedgehog signaling, WNT/β-catenin signaling, mitotic, notch signaling, and TGF-β signaling were the top five pathways positively associated with the risk score. To sum up, AAMRGs were associated with the immune microenvironment of CRC patients and could be applied as biomarkers to predict the prognosis and immunotherapy response of patients.

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Section: Discussionmentioning

confidence: 92%

Amino acid metabolism genes associated with immunotherapy responses and clinical prognosis of colorectal cancer

Peng

Zheng

Guo

et al. 2022

Front. Mol. Biosci.

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“…According to several studies, increased CTL levels in the tumor microenvironment have been linked to antitumor effects and improved prognosis in a variety of malignancies, including CRC. The dMMR group had more CD56+ cells, CD4+ cells, and higher CD8 protein levels than the pMMR group, according to Bai and colleagues [ 39 ]. In the present study, we observed that T cell CD4+ Th1, T cell NK, T cell CD4+ effector memory, T cell CD4+ central memory, and eosinophil cells were enriched in cluster 2 CRC samples.…”

Section: Discussionmentioning

confidence: 97%

Dysregulation of Circadian Clock Genes Associated with Tumor Immunity and Prognosis in Patients with Colon Cancer

Chen

Dai

et al. 2022

Computational and Mathematical Methods in Medicine

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Early research shows that disrupting the circadian rhythm increases the risk of various cancers. However, the roles of circadian clock genes in colorectal cancer, which is becoming more common and lethal in China, remained to be unclear. In conclusion, the present study has demonstrated that multiple CCGs were dysregulated and frequently mutated in CRC samples by analyzing the TCGA database. The higher expression levels of REV1, ADCYAP1, CSNK1D, NR1D1, CSNK1E, and CRY2 had a strong link with shorter DFS time in CRC patients, demonstrating that CCGs had an important regulatory role in CRC development. Moreover, 513 CRC tumor samples were divided into 3 categories, namely, cluster1 ( n = 428 ), cluster2 ( n = 83 ), and cluster 3 ( n = 109 ), based on the expression levels of the CCGs. Clinical significance analysis showed that the overall survival and disease-free survival of cluster 2 and cluster 3 were significantly shorter than those of cluster 1. The stemness scores in cluster 1 and cluster 2 were significantly higher than those of cluster 3 CRC samples. Clinically, we found that the C3 subtype had significantly higher percentage of T3/T4, N1/N2, and grades III and IV than groups C1 or C2. In addition, we reported that different CRC clusters had significantly different tumor-infiltrating immune cell signatures. Finally, pancancer analysis showed that higher expression of CSNK1D was correlated with shorter DFS time in multiple cancer types, such as COAD and LIHC, and was dysregulated in various cancers. In conclusion, we effectively developed a CCG-related predictive model and opened up new avenues for research into immune regulatory mechanisms and the development of immunotherapy for CRC.

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“…However, the predictive potential of PD-L1 expression was not seen in a randomized clinical trial of patients with HR-positive, ERBB2negative mBC (Tolaney et al, 2020). Biomarker analysis indicated that PD-L1 status, TILs, tumor mutation burden (TMB), and genomic alterations were not associated with PFS in the pembrolizumab plus eribulin arm (Tolaney et al, 2020;Bai et al, 2021) (Table 3).…”

Section: Pd-l1 Expressionmentioning

confidence: 99%

Combinatorial Strategies With PD-1/PD-L1 Immune Checkpoint Blockade for Breast Cancer Therapy: Mechanisms and Clinical Outcomes

Zheng

Hou

et al. 2022

Front. Pharmacol.

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As an emerging antitumor strategy, immune checkpoint therapy is one of the most promising anticancer therapies due to its long response duration. Antibodies against the programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) axis have been extensively applied to various cancers and have demonstrated unprecedented efficacy. Nevertheless, a poor response to monotherapy with anti-PD-1/PD-L1 has been observed in metastatic breast cancer. Combination therapy with other standard treatments is expected to overcome this limitation of PD-1/PD-L1 blockade in the treatment of breast cancer. In the present review, we first illustrate the biological functions of PD-1/PD-L1 and their role in maintaining immune homeostasis as well as protecting against immune-mediated tissue damage in a variety of microenvironments. Several combination therapy strategies for the combination of PD-1/PD-L1 blockade with standard treatment modalities have been proposed to solve the limitations of anti-PD-1/PD-L1 treatment, including chemotherapy, radiotherapy, targeted therapy, antiangiogenic therapy, and other immunotherapies. The corresponding clinical trials provide valuable estimates of treatment effects. Notably, several combination options significantly improve the response and efficacy of PD-1/PD-L1 blockade. This review provides a PD-1/PD-L1 clinical trial landscape survey in breast cancer to guide the development of more effective and less toxic combination therapies.

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Tumor-Infiltrating Lymphocytes in Colorectal Cancer: The Fundamental Indication and Application on Immunotherapy

Cited by 64 publications

References 155 publications

Amino acid metabolism genes associated with immunotherapy responses and clinical prognosis of colorectal cancer

Amino acid metabolism genes associated with immunotherapy responses and clinical prognosis of colorectal cancer

Dysregulation of Circadian Clock Genes Associated with Tumor Immunity and Prognosis in Patients with Colon Cancer

Combinatorial Strategies With PD-1/PD-L1 Immune Checkpoint Blockade for Breast Cancer Therapy: Mechanisms and Clinical Outcomes

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