Tumour-infiltrating inflammation and prognosis in colorectal cancer: systematic review and meta-analysis

Mei, Zubing; Liu, Y; Liu, C; Cui, Ang; Liang, Zhuangzhuang; Wang, G; Peng, Huan; Cui, Long; Li, Cong

doi:10.1038/bjc.2014.46

Cited by 278 publications

(244 citation statements)

References 60 publications

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“…9 Previous studies have found that tumors with a high infiltrate of CD8 + cytotoxic T lymphocytes (CTL) and T helper 1 (Th1)-type cells had a more favorable prognosis than those with a low infiltrate. 10,11 Recent publications have demonstrated the high level of tumour-infiltrating T lymphocytes (TIL) is associated with MSI-H features in CRC. 12 Most significantly, CRC tumors with MSI creates a rich abundance of neoantigens responsible for the immune response.…”

Section: Introductionmentioning

confidence: 99%

The comprehensive molecular landscape of the immunologic co-stimulator B7 and TNFR ligand receptor families in colorectal cancer: immunotherapeutic implications with microsatellite instability

Tang

Liu

et al. 2018

OncoImmunology

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Immunotherapy is reportedly effective in a subset of colorectal cancers (CRCs) with high microsatellite instability (MSI-H). Exploring the expression patterns and clinical values of immunologic molecules is critical in defining the specific responsive candidates. Here, we performed comprehensive molecular profiling of the B7 and TNFR family genes across 6 CRC datasets with over 1,000 patients’ details using cBioPortal TCGA data. About 20% of patients had B7 and TNFR family gene alterations. The frequency of B7 gene mutations (2.2%–5%) were similar to copy number alterations (0.53%–5.46%). TNFR amplifications were relatively more common (5.45–11.32%) than that of B7 (0.09–2.73%). B7 and TNFR gene mRNAs were upregulated in 26% of cases (102/379) and 16% of cases (61/379), respectively. The mRNA levels of B7 and TNFR genes were inversely correlated with promoter methylation status. Clinically, both B7-H3 and TNFSF7 mRNA overexpression were associated with unfavorable clinical outcomes, and the B7-H3 expression was increased gradually in cases with gene amplifications. Moreover, patients with MSI-H had significantly higher PD-L1 or PD-1 expression. Most importantly, in MSI-H group, patients with PD-L1 or PD-1 upregulation had poorer survivals than those with PD-L1/PD-1 downregulation. This is the first study drawing the immune landscapes of the co-stimulator B7 and TNFR families in CRC and showing that MSI-H patients with PD-1/PD-L1 upregulation are associated with poor clinical outcomes, providing potential markers to stratify patients responsive to immune checkpoint therapy.

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Section: Introductionmentioning

confidence: 99%

The comprehensive molecular landscape of the immunologic co-stimulator B7 and TNFR ligand receptor families in colorectal cancer: immunotherapeutic implications with microsatellite instability

Tang

Liu

et al. 2018

OncoImmunology

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“…12,13 Although tumor-infiltrating T lymphocytes have implications for tumor prognosis, information on the TCR diversity of HBV-associated liver cancer remains limited. [14][15][16] A recent investigation of HBV-associated HCC indicated that the highly expanded clone (HEC) ratio of TCRb CDR3 (TRB CDR3) was significantly different in liver cancer compared to healthy and hepatitis B patients. 17 The comparison of TRB CDR3 among three histological types of liver cancer samples revealed that the consistency between tumor tissues and adjacent non-tumor tissues was related to tumor malignancy.…”

Section: Introductionmentioning

confidence: 99%

High-throughput T cell receptor sequencing reveals distinct repertoires between tumor and adjacent non-tumor tissues in HBV-associated HCC

Chen

Zhao

et al. 2016

OncoImmunology

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T lymphocytes, which recognize antigen peptides through specific T cell receptors (TCRs), play an important role in the human adaptive immune response. TCR diversity is closely associated with host immune response and cancer prognosis. Although tumor-infiltrating T lymphocytes have implications for tumor prognosis, few studies have performed a detailed characterization of TCR diversity in both tumor and non-tumor tissues in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). Here, we performed high-throughput sequencing of the TCRb chain complementarity determining region 3 (CDR3) of liver-infiltrating T cells from 48 HBV-associated HCC patients. A significantly higher average number of CDR3 aa clonotypes (2259 vs. 1324, p < 0.001), and significantly higher TCR diversity (Gini coefficient, p < 0.001; Simpson index, p < 0.01; Shannon entropy, p < 0.001) were observed in tumor tissues compared with adjacent non-tumor tissues. The ratio of highly expanded clones (HECs) was significantly higher in non-tumor tissues than in tumor tissues when the HEC threshold was defined as 2% or greater (p < 0.05). Our analysis of the median Morisita-Horn index indicated weak TCR repertoire similarity between tumor and matched non-tumor tissues. The median number of shared clones in tumor tissue and matched non-tumor tissue from each patient was 360.5, representing 5.1-15.8% (10.6 § 0.4%) of all clones in each patient. We observed extensive heterogeneity of T lymphocytes in tumors and higher HEC ratios in adjacent non-tumor tissues of HCC patients. The differential T cell repertoires in tumor and non-tumor tissues suggest a distinct T cell immune microenvironment in patients with HBV-associated HCC.

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“…Regulatory T cells can also suppress the function of cytotoxic CD8-positive T cells, thus inhibiting anti-tumor immune responses, largely through a mechanism that requires cell-cell contact. CD8-positive T cells are generally thought to play a central role in anti-tumor immune responses and the presence of CD8-positive T cells has been reported as a prognostic factor [38][39][40][41][42][43][44]. In our study, we observed an inverse correlation between PD-L overexpression in the tumors and CD8-positive T lymphocyte infiltration mainly in patients with late stage cancers indicating that PD-L expression can negatively influence the presence of CD8-positive T cells.…”

Section: Discussionmentioning

confidence: 99%

Clinical Significance and Therapeutic Potential of the Programmed Death Ligand-1 (PD-L1) and PD-L2 Expression in Human Colorectal Cancer

Gasser¹,

Koenigshausen²,

Grimm³

et al. 2017

J Cancer Sci Ther

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Purpose: The programmed death-1/programmed death ligand (PD-1/PD-L) pathway in T cell activation has been shown to play an important role in tumor evasion from host immunity. The predictive value of PD-L1 and PD-L2 expression in colorectal cancer (CRC) remains still under discussion. We analyzed whether negative signaling of infiltrating PD-1-positive T cells through PD-L1 and PD-L2 within the tumor could promote further tumor progression through downregulation of anti-tumor immunity. Methods:We investigated PD-L1 and PD-L2 expression in tumors from patients with CRC and analyzed its prognostic significance with respect to outcome analysis. Conclusion:The presented results from primary tumors and CRC patient outcome analysis suggest that negative signaling of infiltrating PD-1-positive T cells through PD-L1 expression within the tumor may promote further tumor progression through downregulation of anti-tumor immunity. Co-expression of PD-1 on CD4/Foxp3-positive T cells was found indicating T regulatory cell-mediated mechanisms by which tumor cells can evade immune recognition and destruction. This study demonstrates the importance of strategies inhibiting negative PD-1/ PD-L1 signaling in CRC.

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Tumour-infiltrating inflammation and prognosis in colorectal cancer: systematic review and meta-analysis

Cited by 278 publications

References 60 publications

The comprehensive molecular landscape of the immunologic co-stimulator B7 and TNFR ligand receptor families in colorectal cancer: immunotherapeutic implications with microsatellite instability

The comprehensive molecular landscape of the immunologic co-stimulator B7 and TNFR ligand receptor families in colorectal cancer: immunotherapeutic implications with microsatellite instability

High-throughput T cell receptor sequencing reveals distinct repertoires between tumor and adjacent non-tumor tissues in HBV-associated HCC

Clinical Significance and Therapeutic Potential of the Programmed Death Ligand-1 (PD-L1) and PD-L2 Expression in Human Colorectal Cancer

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