scholarly journals Lipidomic Typing of Colorectal Cancer Tissue Containing Tumour-Infiltrating Lymphocytes by MALDI Mass Spectrometry Imaging

Metabolites ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 599
Author(s):  
Vanna Denti ◽  
Allia Mahajneh ◽  
Giulia Capitoli ◽  
Francesca Clerici ◽  
Isabella Piga ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Lymphocytes ◽  
Tumour Microenvironment ◽  
Maldi Mass Spectrometry ◽  
Cancer Tissue ◽  
Human Thymus ◽  
Molecular Approaches ◽  
Starting Point ◽  
Tumour Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes

Predicting the prognosis of colorectal cancer (CRC) patients remains challenging and a characterisation of the tumour immune environment represents one of the most crucial avenues when attempting to do so. For this reason, molecular approaches which are capable of classifying the immune environments associated with tumour infiltrating lymphocytes (TILs) are being readily investigated. In this proof of concept study, we aim to explore the feasibility of using spatial lipidomics by MALDI-MSI to distinguish CRC tissue based upon their TIL content. Formalin-fixed paraffin-embedded tissue from human thymus and tonsil was first analysed by MALDI-MSI to obtain a curated mass list from a pool of single positive T lymphocytes, whose putative identities were annotated using an LC-MS-based lipidomic approach. A CRC tissue microarray (TMA, n = 30) was then investigated to determine whether these cases could be distinguished based upon their TIL content in the tumour and its microenvironment. MALDI-MSI from the pool of mature T lymphocytes resulted in the generation of a curated mass list containing 18 annotated m/z features. Initially, subsets of T lymphocytes were then distinguished based on their state of maturation and differentiation in the human thymus and tonsil tissue. Then, when applied to a CRC TMA containing differing amounts of T lymphocyte infiltration, those cases with a high TIL content were distinguishable from those with a lower TIL content, especially within the tumour microenvironment, with three lipid signals being shown to have the greatest impact on this separation (p < 0.05). On the whole, this preliminary study represents a promising starting point and suggests that a lipidomics MALDI-MSI approach could be a promising tool for subtyping the diverse immune environments in CRC.

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

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 Immune Classification for the PD-L1 Expression and Tumour-Infiltrating Lymphocytes in Colorectal Adenocarcinoma

2019 ◽  
Author(s):  
Byeong-Joo Noh ◽  
Jae Young Kwak ◽  
Dae-Woon Eom
Keyword(s):  
Colorectal Adenocarcinoma ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Tumour Microenvironment ◽  
Tumour Cells ◽  
Effective Response ◽  
Recent Emergence ◽  
Tumour Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes ◽  
Colorectal Adenocarcinomas

Abstract Background Colorectal adenocarcinoma is the third most common cancer worldwide and a leading cause of cancer-related death. The recent emergence of diverse immunotherapeutic agents has made it crucial to interpret a complex tumour microenvironment intermingled with tumour-infiltrating immune cells to predict the immunotherapeutic response rate. However, in colorectal adenocarcinoma, studies are lacking that provide detailed analyses of programmed death-ligand 1 (PD-L1) and tumour-infiltrating lymphocytes (TIL) to elucidate their prognostic values and to identify immunotherapy-targetable subgroups, preferably with multiple immune-related biomarkers. In the present study, we categorize colorectal adenocarcinomas into four types of tumour immune microenvironments according to PD-L1 expression and TIL, analyse their prognostic values, and propose an immunotherapy-targetable subgroup.Methods Formalin-fixed, paraffin-embedded tissue samples of surgically resected primary colorectal adenocarcinomas (n = 489) were obtained and arrayed on tissue microarray blocks. Immunohistochemical stains for PD-L1, programmed cell death protein 1 (PD-1), cluster of differentiation 8 (CD8), and microsatellite instability (MSI) were performed and evaluated.Results Tumour microenvironment immune type (TMIT) I (PD-L1-positive tumour cells and CD8-high TIL) and type II (PD-L1-negative tumour cells and CD8-low TIL) showed the best and worst prognoses, respectively. PD-L1 overexpression was significantly associated with MSI status. PD-L1 immunoreactivity was positively correlated with TIL having CD8 or PD-1 overexpression.Conclusions TMIT I subgroup showed stronger CD8/PD-L1/PD-1 signalling interaction compared to the other TMIT. Therefore, we propose that the TMIT I subgroup is a candidate TMIT to predict effective response rate for existing immune checkpoint inhibitors and determine targetable subgroups for emerging therapies.

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.

scholarly journals CD8+ Tumour-Infiltrating Lymphocytes and Tumour Microenvironment Immune Types as Biomarkers for Immunotherapy in Sinonasal Intestinal-Type Adenocarcinoma

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 202
Author(s):  
Rocío García-Marín ◽  
Sara Reda ◽  
Cristina Riobello ◽  
Virginia N. Cabal ◽  
Laura Suárez-Fernández ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Value ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Tumour Microenvironment ◽  
Intestinal Type ◽  
Rare Tumour ◽  
Intestinal Type Adenocarcinoma ◽  
Tumour Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes

Background. Intestinal-type adenocarcinoma (ITAC) is a rare tumour occurring in the ethmoid sinus. Recent years have brought advances in endoscopic surgery and precision radiotherapy; however, five-year overall survival has not improved and remains at 35–80%, depending on tumour stage and histology. Therefore, there is a need for new therapeutic options. Methods. We evaluated CD8+ tumour-infiltrating lymphocytes (TILs) and tumour microenvironment immune type (TMIT, combining CD8+ TILs and PD-L1) as predictive biomarkers for immunotherapy in a series of 133 ITAC. All results were correlated to clinical and follow-up data. Results. The presence of intratumoural CD8+ TILs was low in 57% of cases and high in 8% of cases. Tumoural PD-L1 positivity was observed in 26% of cases. CD8+ TILs and TMIT correlated with the histological subtype of ITAC and with better overall survival. The presence of stromal PD-L1-positive macrophages was related to intratumoural CD8+ TILs. PD-L1 expression on tumour cells or macrophages did not show prognostic value. Conclusions. TMIT classification did not have additional prognostic value over CD8+ TILs alone. The modest percentage of CD8high/PD-L1pos cases indicates that ITAC is a lowly immunogenic tumour type. Nevertheless, a proportion of ITAC, especially the papillary and colonic subtypes, could benefit from therapy with immune checkpoint inhibitors.

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