Characterization of tumour-infiltrating lymphocytes and apoptosis in colitis-associated neoplasia: comparison with sporadic colorectal cancer

2006 ◽  
Vol 208 (3) ◽  
pp. 381-387 ◽  
Author(s):  
JM Michael-Robinson ◽  
N Pandeya ◽  
MD Walsh ◽  
A-E Biemer-Huttmann ◽  
RD Eri ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Sporadic Colorectal Cancer ◽  
Tumour Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes

Tumour-infiltrating lymphocytes in colorectal cancer with microsatellite instability are activated and cytotoxic

2004 ◽  
Vol 91 (4) ◽  
pp. 469-475 ◽  
Author(s):  
S. M. Phillips ◽  
A. Banerjea ◽  
R. Feakins ◽  
S. R. Li ◽  
S. A. Bustin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Tumour Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes

scholarly journals Characterization of rare transformingKRASmutations in sporadic colorectal cancer

2014 ◽  
Vol 15 (6) ◽  
pp. 768-776 ◽  
Author(s):  
Joanna HM Tong ◽  
Raymond WM Lung ◽  
Frankie MC Sin ◽  
Peggy PY Law ◽  
Wei Kang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Sporadic Colorectal Cancer

Prognostic value of tumour-infiltrating lymphocytes (TILs) in colorectal cancer

1997 ◽  
Vol 182 (3) ◽  
pp. 318-324 ◽  
Author(s):  
Kirsi M. Ropponen ◽  
Matti J. Eskelinen ◽  
Pertti K. Lipponen ◽  
Esko Alhava ◽  
Veli-Matti Kosma
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Value ◽  
Tumour Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes

scholarly journals Significant and conflicting correlation of IL-9 with Prevotella and Bacteroides in human colorectal cancer

2020 ◽  
Author(s):  
E Niccolai ◽  
E Russo ◽  
S Baldi ◽  
F Ricci ◽  
G Nannini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Multinomial Regression ◽  
Tnf Α ◽  
Ifn Γ ◽  
Inflammatory Profile ◽  
Infiltrating Lymphocytes ◽  
First Time

ABSTRACTBackgroundColorectal cancer (CRC) is a widespread disease that represents an example of chronic inflammation-associated tumor. In fact, the immune system, besides protecting the host from developing tumors, can support the CRC progression. In this scenario, the gut microbiota (GM) is essential to modulate immune responses and a dysbiotic condition can favor chronic/abnormal immune activation that support the tumor growth. GM can elicit the production of cytokines, influencing the immunostimulatory or immunosuppressive reactions, such as the tendency to mount Th1, Th17, Tregs or Th9 responses that play different roles towards colon cancer. Paradigmatic is the role of IL-9 that can both promote tumor progression in hematological malignancies and inhibit tumorigenesis in solid cancers. Therefore, to investigate the microbiota-immunity axis in CRC patients is crucial to well understand the cancer development with positive relapses in prevention and treatment.AimThe cellular and molecular characterization of the immune response and the evaluation of GM composition in healthy and tumor mucosa, focusing on the correlation between cytokines’ profile and GM signature.MethodsWe collected tumoral (CRC) and healthy (CRC-S) mucosa samples of 45 CRC patients. For each sample, we characterized the Tissue Infiltrating Lymphocytes (TIL)’s subset profile and the GM composition. In addition, in 14 CRC patients, we evaluated the CRC and CRC-S molecular inflammatory response (26 cytokines/chemokines) and we correlated this profile with GM composition using the Dirichlet Multinomial Regression.ResultsThe analysis of T cells subsets distribution showed that CRC samples displayed higher percentages of Th17, Th2, Tregs, Tc17, Tc1/Tc17, and Tcreg, compared to CRC-S. Notably, also the number of Th9 was higher, even if not significantly, in CRC tissue compared to healthy one. In addition, we found that MIP-1α, IL-1β, IL-2, IP-10, IL-6, IL-8, IL-17A, IFN-γ, TNF-α, MCP-1, IL-1α, P-selectin and IL-9 were significantly increased in CRC compared to CRC-S. Moreover, the GM analysis revealed that CRC samples had significantly higher levels of Fusobacteria, Proteobacteria, Fusobacterium, Ruminococcus2 (Lachnospiraceae family) and Ruminococcus (Ruminococcaceae family) than CRC-S. Finally, we found that the abundance of Prevotella spp in CRC samples was negatively correlated with IL-17A and positively with IL-9. In addition, the abundance of Bacteroides and Escherichia/Shigella species in CRC samples showed a negative association with IL-9 and IP-10 respectively.ConclusionsOur data show a clear dissimilarity of inflammatory profile and GM composition between the tumor and the adjacent healthy tissue, displaying the generation of a peculiar CRC microenvironment. Interestingly, relating the tissue cytokine profile with the GM composition, we confirmed the presence of a bidirectional crosstalk between the immune response and the host’s commensal microorganisms; in detail, we documented for the first time that Prevotella spp. and Bacteroides spp. are correlated (positively and negatively, respectively) with the IL-9, whose role in CRC development is still debated.

scholarly journals O66: FLOW CYTOMETRIC AND RNA SEQUENCED UNCOUPLING OF TUMOUR-INFILTRATING LYMPHOCYTE CHECKPOINT EXPRESSION AND MISMATCH REPAIR STATUS IN COLORECTAL CANCER

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
A Zaborowski ◽  
C Harmon ◽  
D Duquette ◽  
L Dyck ◽  
L Lynch ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Functional Status ◽  
Mismatch Repair ◽  
T Cell Response ◽  
Checkpoint Blockade ◽  
Colonic Tissue ◽  
Flow Cytometric ◽  
Tumour Infiltrating Lymphocytes ◽  
Mismatch Repair Status ◽  
Infiltrating Lymphocytes

Abstract Introduction Selection criteria for immunotherapy with checkpoint blockade in colorectal cancer are currently based on mismatch repair status. However, intra-tumoral T cell response varies among patients with the same MMR status. Inhibitory checkpoint expression on tumour-infiltrating lymphocytes in microsatellite stable and unstable CRC is unknown. Method Flow cytometric analysis and single-cell RNA sequencing, using the 10x genomic platform, were performed ex vivo on tumour and uninvolved colonic tissue samples from patients undergoing surgical resection for colorectal cancer. Inhibitory checkpoint expression (PD-1) and functional status of isolated populations of TILs were analysed. Result Conventional and unconventional tissue-resident T cells were enriched in tumour samples compared to uninvolved healthy colonic tissue. Upregulation of PD-1 expression on TILs was observed in all patients, however the % upregulation varied among those with the same MMR status. A proportion of MSS tumours were found to have high levels of PD-1 expression, while a subset of MSI tumours had low PD-1 expression. Functional studies of cytotoxicity demonstrated varying TIL production of IFNg, TNFa and amphiregulin in patients with the same MMR status. Conclusion TIL profile (infiltration pattern, checkpoint expression and functional status) differs among patients with the same MMR status. A subset of ‘hot’ immunogenic MSS tumours exist that may respond to checkpoint blockade. Characterisation of TIL profile represents a more accurate method of selecting patients likely to derive benefit. Abbrev. CRC Colorectal cancer, MMR Mismatch repair, TIL Tumour-infiltrating lymphocytes, MSS Microsatellite stable, MSI Microsatellite unstable, IFNg Interferon-gamma, TNFa Tumour necrosis factor alpha Take-home message A subset of immunogenic microsatellite stable colorectal tumours exist that may respond to checkpoint blockade. Mismatch repair status alone does not accurately predict response to immunotherapy.

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