12‐Chemokine signature, a predictor of tumor recurrence in colorectal cancer

Tokunaga, Ryuma; Nakagawa, Shigeki; Sakamoto, Yasuo; Nakamura, Kenichi; Naseem, Madiha; Izumi, Daisuke; Kosumi, Keisuke; Taki, Katsunobu; Higashi, Taishi; Miyata, Tatsunori; Miyamoto, Yuji; Yoshida, Naoya; Baba, Hideo; Lenz, Heinz‐Josef

doi:10.1002/ijc.32982

Cited by 46 publications

(47 citation statements)

References 42 publications

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“…In stages II/III CRC, TLS and especially mature TLS are increased in MSI positive tumors and correlate with a better outcome compared with immature TLS ( 22 , 50 ). Similar results were obtained using a 12-chemokine signature on fixed tissues or through TCGA database rather than immunohistochemistry as hallmark of TLS ( 38 , 40 ), indicating that different approaches can be used for TLS quantification.…”

Section: Importance Of the Organization Of Tumor-infiltrating Immune Cells In Tumor Immunosurveillancesupporting

confidence: 68%

“…Mutations of BRAF are detected in several solid cancers, such as NSCLC, melanoma, and colorectal cancers. In CRC, BRAF mutations are associated with a higher TLS density, and TLS are more mature compared with BRAF wild type (wt) tumors ( 22 , 40 ). Surprisingly, little is known regarding the relationship between BRAF mutations and TLS presence in melanoma, although patients have benefited from anti-BRAF targeted therapies for nearly ten years.…”

Section: Importance Of the Organization Of Tumor-infiltrating Immune Cells In Tumor Immunosurveillancementioning

confidence: 99%

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Tumor-Associated Tertiary Lymphoid Structures: From Basic and Clinical Knowledge to Therapeutic Manipulation

et al. 2021

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The tumor microenvironment is a complex ecosystem almost unique to each patient. Most of available therapies target tumor cells according to their molecular characteristics, angiogenesis or immune cells involved in tumor immune-surveillance. Unfortunately, only a limited number of patients benefit in the long-term of these treatments that are often associated with relapses, in spite of the remarkable progress obtained with the advent of immune checkpoint inhibitors (ICP). The presence of “hot” tumors is a determining parameter for selecting therapies targeting the patient immunity, even though some of them still do not respond to treatment. In human studies, an in-depth analysis of the organization and interactions of tumor-infiltrating immune cells has revealed the presence of an ectopic lymphoid organization termed tertiary lymphoid structures (TLS) in a large number of tumors. Their marked similarity to secondary lymphoid organs has suggested that TLS are an “anti-tumor school” and an “antibody factory” to fight malignant cells. They are effectively associated with long-term survival in most solid tumors, and their presence has been recently shown to predict response to ICP inhibitors. This review discusses the relationship between TLS and the molecular characteristics of tumors and the presence of oncogenic viruses, as well as their role when targeted therapies are used. Also, we present some aspects of TLS biology in non-tumor inflammatory diseases and discuss the putative common characteristics that they share with tumor-associated TLS. A detailed overview of the different pre-clinical models available to investigate TLS function and neogenesis is also presented. Finally, new approaches aimed at a better understanding of the role and function of TLS such as the use of spheroids and organoids and of artificial intelligence algorithms, are also discussed. In conclusion, increasing our knowledge on TLS will undoubtedly improve prognostic prediction and treatment selection in cancer patients with key consequences for the next generation immunotherapy.

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Section: Importance Of the Organization Of Tumor-infiltrating Immune Cells In Tumor Immunosurveillancesupporting

confidence: 68%

Section: Importance Of the Organization Of Tumor-infiltrating Immune Cells In Tumor Immunosurveillancementioning

confidence: 99%

Tumor-Associated Tertiary Lymphoid Structures: From Basic and Clinical Knowledge to Therapeutic Manipulation

et al. 2021

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“…TLS have been detected in numerous tumor types using immunohistochemistry or chemokine gene signatures which tightly correlated with the presence of TLS identified by immunochemistry. 41,[50][51][52] In particular, a 12-chemokine gene signature was correlated to increased survival in melanoma, 50 colorectal 51,52 and breast 53 cancers. In addition, other gene signatures containing 8 and 19 genes related to the presence of T follicular helper cells, type 1 helper CD4 + T cells and B cells were reported in breast 54 and gastric 55 cancers.…”

Section: Tertiary Lymphoid Structures In Cancerprognostic and Predictmentioning

confidence: 99%

Tertiary lymphoid structures and B lymphocytes in cancer prognosis and response to immunotherapies

et al. 2021

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Tertiary lymphoid structures (TLS) are ectopic cellular aggregates that resemble secondary lymphoid organs in their composition and structural organization. In contrast to secondary lymphoid organs, TLS are not imprinted during embryogenesis but are formed in non-lymphoid tissues in response to local inflammation. TLS structures exhibiting a variable degree of maturation are found in solid tumors. They are composed of various immune cell types including dendritic cells and antigen-specific B and T lymphocytes, that together, actively drive the immune response against tumor development and progression. This review highlights the successive steps leading to tumor TLS formation and its association with clinical outcomes. We discuss the role played by tumor-infiltrating B lymphocytes and plasma cells, their prognostic value in solid tumors and immunotherapeutic responses and their potential for future targeting.

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“…Using immune and in ammatory cells, Xiao G et al constructed a risk signature for assessing e ciency of chemotherapy and distant metastases of CRC [37]. Tokunaga R et al presented a 12-chemokine signature for evaluating tumor recurrence in CRC [38]. Zong Z et al demonstrated a prognostic alternative splicing signature by differential splicing patterns of 13 genes in CRC [39].…”

Section: Based On the Strati Cation Of Clinical Variables The Correlmentioning

confidence: 99%

A Novel Ferroptosis-related Lncrna Prognostic Signature for Colorectal Cancer by Bioinformatics Analysis

Yang

Zhang

Wang

et al. 2021

Preprint

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Background: Recently, extensive studies have shown that ferroptosis in cancer treatment has been increasingly confirmed. The current study aims to construct a robust ferroptosis-related lncRNAs signature prediction model of colorectal cancer (CRC) patients by bioinformatics analysisMethods: The transcriptome data were abstracted from The Cancer Genome Atlas (TCGA). Differentially expressed lncRNAs were screened by comparing 568 CRC tissues with 44 adjacent non-CRC tissues. Univariate Cox regression, lasso regression, multivariate Cox regression were conducted to design a ferroptosis-related lncRNA signature. This signature’s prognosis was verified by the log-rank test of Kaplan-Meier curve and the area under curve (AUC) of receiver operating characteristic (ROC) in train set, test set, and entire set. Furthermore, univariate and multivariate Cox regression were used to analyze its independent prognostic ability. The relationship of the ferroptosis-linked lncRNAs' expression and clinical variables was demonstrated by Wilcoxon rank-sum test and Kruskal-Wallis test. Gene set enrichment analysis (GSEA) was performed to signaling pathways it may involve.Results: 2541 differentially expressed lncRNAs were screened, of which 439 are ferroptosis-related lncRNAs. A seven ferroptosis-related lncRNAs (AC005550.2, LINC02381, AL137782.1, C2orf27A, AC156455.1, AL354993.2, AC008760.1) prognostic signature was constructed, validated and evaluated. This model's prognosis in the high-risk group is obviously worse than that of the low-risk group in train set, test set, and entire set. The AUC of ROC predicting the three years survival in the train set, test set, and entire set was 0.796, 0.715, and 0.758, respectively. Moreover, the designed molecular signature was found to be an independent prognostic variable. Compared to clinical variables, this signature's ROC curves demonstrated the second largest AUC value (0.737). The expression of these lncRNAs and the lncRNA signature are related to distant metastasis, Lymph-node status, clinical stage, T stage, KRAS mutation, BRAF mutation, MMR status, and perineural invasion. Finally, GSEA analysis results show that the signature is involved in six metabolism-related pathways.Conclusion: The current study constructed, validated, and evaluated a seven ferroptosis-related lncRNA signature which can independently be used to predict the prognosis of CRC patients, and it may become a new therapeutic target.

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12‐Chemokine signature, a predictor of tumor recurrence in colorectal cancer

Cited by 46 publications

References 42 publications

Tumor-Associated Tertiary Lymphoid Structures: From Basic and Clinical Knowledge to Therapeutic Manipulation

Tumor-Associated Tertiary Lymphoid Structures: From Basic and Clinical Knowledge to Therapeutic Manipulation

Tertiary lymphoid structures and B lymphocytes in cancer prognosis and response to immunotherapies

A Novel Ferroptosis-related Lncrna Prognostic Signature for Colorectal Cancer by Bioinformatics Analysis

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