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 Association between Microsatellite Instability Status and Peri-Operative Release of Circulating Tumour Cells in Colorectal Cancer

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 425 ◽  
Author(s):  
James W. T. Toh ◽  
Stephanie H. Lim ◽  
Scott MacKenzie ◽  
Paul de Souza ◽  
Les Bokey ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Venous Blood ◽  
Peripheral Circulation ◽  
Curative Intent ◽  
Mean Values ◽  
Time Points ◽  
Significant Difference ◽  
Circulating Tumour Cell ◽  
Infiltrating Lymphocytes

Microsatellite instability (MSI) in colorectal cancer (CRC) is a marker of immunogenicity and is associated with an increased abundance of tumour infiltrating lymphocytes (TILs). In this subgroup of colorectal cancer, it is unknown if these characteristics translate into a measurable difference in circulating tumour cell (CTC) release into peripheral circulation. This is the first study to compare MSI status with the prevalence of circulating CTCs in the peri-operative colorectal surgery setting. For this purpose, 20 patients who underwent CRC surgery with curative intent were enrolled in the study, and peripheral venous blood was collected at pre- (t1), intra- (t2), immediately post-operative (t3), and 14–16 h post-operative (t4) time points. Of these, one patient was excluded due to insufficient blood sample. CTCs were isolated from 19 patients using the IsofluxTM system, and the data were analysed using the STATA statistical package. CTC number was presented as the mean values, and comparisons were made using the Student t-test. There was a trend toward increased CTC presence in the MSI-high (H) CRC group, but this was not statistically significant. In addition, a Poisson regression was performed adjusting for stage (I-IV). This demonstrated no significant difference between the two MSI groups for pre-operative time point t1. However, time points t2, t3, and t4 were associated with increased CTC presence for MSI-H CRCs. In conclusion, there was a trend toward increased CTC release pre-, intra-, and post-operatively in MSI-H CRCs, but this was only statistically significant intra-operatively. When adjusting for stage, MSI-H was associated with an increase in CTC numbers intra-operatively and post-operatively, but not pre-operatively.

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

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

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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