0000000000005445
AUTHOR
Juha P. Väyrynen
showing 13 related works from this author
Stromal hyaluronan accumulation is associated with low immune response and poor prognosis in pancreatic cancer
2021
AbstractHyaluronan (HA) accumulation has been associated with poor survival in various cancers, but the mechanisms for this phenomenon are still unclear. The aim of this study was to investigate the prognostic significance of stromal HA accumulation and its association with host immune response in pancreatic ductal adenocarcinoma (PDAC). The study material consisted of 101 radically treated patients for PDAC from a single geographical area. HA staining was evaluated using a HA-specific probe, and the patterns of CD3, CD8, CD73 and PD-L1 expression were evaluated using immunohistochemistry. HA staining intensity of tumour stromal areas was assessed digitally using QuPath. CD3- and CD8-based …
Immune Contexture of MMR-Proficient Primary Colorectal Cancer and Matched Liver and Lung Metastases
2021
Simple Summary Metastasis is the main cause for cancer mortality. The most common metastatic sites of colorectal cancer (CRC) are the liver and lungs. Tumour-infiltrating lymphocytes are recognized as beneficial prognostic factors both in primary and metastatic CRC, but less is known about their reciprocal differences. The aim of our study was to evaluate immune microenvironment and its prognostic value in a series of mismatch proficient (pMMR) CRC with matched liver and lung metastases. The proportion of tumours with high immune cell infiltration together with PD-L1-positivity almost doubled in metastases compared to primary tumours. Our study confirmed the prognostic value of high ICS in …
The prognostic role of tumor budding and tumor-stroma ratio in pulmonary metastasis of colorectal carcinoma
2023
Objective To evaluate the prognostic value of tumor budding and tumor-stroma ratio (TSR) in resected pulmonary metastases of colorectal carcinoma (CRC). Methods In total, 106 pulmonary metastasectomies were performed to 74 patients in two study hospitals during 2000–2020. All relevant clinical data were retrospectively collected. Tumor budding based on the International Tumor Budding Consensus Conference recommendations and TSR in the first resected pulmonary metastases and primary tumors were evaluated from diagnostic hematoxylin-eosin-stained histopathological slides. Results 60 patients (85.7%) had low tumor budding (≤5 buds/field) and 10 patients (14.3%) had high tumor budding (>5 buds/…
Immunological and prognostic significance of tumour necrosis in colorectal cancer
2023
Abstract Background Colorectal cancer (CRC) causes the second most cancer deaths worldwide, but the disease course varies according to tumour characteristics and immunological factors. Our objective was to examine the associations of tumour necrosis with tumour characteristics, immune cell infiltrates, serum cytokine concentrations, as well as prognosis in CRC. Methods Three independent CRC cohorts, including 1413 patients, were analysed. Associations of the areal percentage of tumour necrosis with clinicopathologic parameters, tumour infiltrating immune cells, cytokine concentrations in systemic and mesenteric vein blood, and survival were examined. Results Higher tumour necrosis percentag…
Immunophenotype based on inflammatory cells, PD-1/PD-L1 signalling pathway and M2 macrophages predicts survival in gastric cancer
2020
Abstract Background Immune response against cancer has prognostic impact but its role in gastric cancer is poorly known. The aim of the study was to assess the prognostic significance of immune cell score (CD3+, CD8+), tumour immune escape (PD-L1, PD-1) and immune tolerance (Clever-1). Methods After exclusion of Epstein-Barr virus positive (n = 4) and microsatellite instable (n = 6) tumours, the study included 122 patients with GC undergoing D2 gastrectomy. CD3+ and CD8+ based ICS, PD-L1, PD-1 and Clever-1 expressions were evaluated. Differences in survival were examined using Cox regression adjusted for confounders. The primary outcome was 5-year survival. Results The 5-year overall surviv…
Immune cell score, PD-L1 expression and prognosis in esophageal cancer.
2021
Esophageal cancer (EC) is the ninth most common cancer worldwide and the sixth leading cause of cancer death [1]. Despite improvements in the treatment of EC, the general outcome remains poor [2–4]...
Tertiary lymphoid structures in pulmonary metastases of microsatellite stable colorectal cancer
2023
Tertiary lymphoid structures (TLSs) are ectopic lymphoid aggregates located at sites of chronic inflammation and recognized as prognosticators in several cancers. We aimed to analyse the prognostic effect of TLSs in colorectal cancer (CRC) pulmonary metastases and primary tumours, with a comparison to the CD3+ and CD8+ cell density-based immune cell score (ICS). For TLS density and TLS maximum diameter analysis, 67 pulmonary metastases and 63 primary tumours were stained with haematoxylin and eosin. For ICS scoring and analysis, CD3 and CD8 immunohistochemistry was performed. Excellent interobserver agreement was achieved in all TLS measurements. Of all patients, 36 patients had low TLS den…
Prognostic significance of spatial and density analysis of T lymphocytes in colorectal cancer.
2022
Abstract Background Although high T cell density is a strong favourable prognostic factor in colorectal cancer, the significance of the spatial distribution of T cells is incompletely understood. We aimed to evaluate the prognostic significance of tumour cell-T cell co-localisation and T cell densities. Methods We analysed CD3 and CD8 immunohistochemistry in a study cohort of 983 colorectal cancer patients and a validation cohort (N = 246). Individual immune and tumour cells were identified to calculate T cell densities (to derive T cell density score) and G-cross function values, estimating the likelihood of tumour cells being co-located with T cells within 20 µm radius (to derive T cell p…
CD3+ and CD8+ T-Cell-Based Immune Cell Score and PD-(L)1 Expression in Pulmonary Metastases of Microsatellite Stable Colorectal Cancer
2022
Simple Summary The lung is the second most common site of metastases in colorectal cancer (CRC). The aim of our study was to evaluate the prognostic value of CD3+ and CD8+ T-cell density based immune cell score (ICS) and PD-1/PD-L1 expression in resected pulmonary metastases of microsatellite stable CRC. The T-cell infiltration was higher in the first pulmonary metastases compared to primary tumour. Pulmonary metastases with high ICS had improved survival compared to low ICS after adjusting for confounders. High tumour cell PD-L1 expression was associated with favourable prognosis. Our results might have clinical feasibility in planning future therapies. Abstract The objective of this study…
Domain-specific transfer learning in the automated scoring of tumor-stroma ratio from histopathological images of colorectal cancer
2023
Tumor-stroma ratio (TSR) is a prognostic factor for many types of solid tumors. In this study, we propose a method for automated estimation of TSR from histopathological images of colorectal cancer. The method is based on convolutional neural networks which were trained to classify colorectal cancer tissue in hematoxylin-eosin stained samples into three classes: stroma, tumor and other. The models were trained using a data set that consists of 1343 whole slide images. Three different training setups were applied with a transfer learning approach using domain-specific data i.e. an external colorectal cancer histopathological data set. The three most accurate models were chosen as a classifie…
A pan-cancer analysis shows immunoevasive characteristics in NRF2 hyperactive squamous malignancies
2023
The NRF2 pathway is frequently activated in various cancer types, yet a comprehensive analysis of its effects across different malignancies is currently lacking. We developed a NRF2 activity metric and utilized it to conduct a pan-cancer analysis of oncogenic NRF2 signaling. We identified an immunoevasive phenotype where high NRF2 activity is associated with low interferon-gamma (IFNγ), HLA-I expression and T cell and macrophage infiltration in squamous malignancies of the lung, head and neck area, cervix and esophagus. Squamous NRF2 overactive tumors comprise a molecular phenotype with SOX2/TP63 amplification, TP53 mutation and CDKN2A loss. These immune cold NRF2 hyperactive diseases are a…
Spatially resolved multimarker evaluation of CD274 (PD-L1)/PDCD1 (PD-1) immune checkpoint expression and macrophage polarisation in colorectal cancer
2023
Abstract Background The CD274 (PD-L1)/PDCD1 (PD-1) immune checkpoint interaction may promote cancer progression, but the expression patterns and prognostic significance of PD-L1 and PD-1 in the colorectal cancer microenvironment are inadequately characterised. Methods We used a custom 9-plex immunohistochemistry assay to quantify the expression patterns of PD-L1 and PD-1 in macrophages, T cells, and tumour cells in 910 colorectal cancer patients. We evaluated cancer-specific mortality according to immune cell subset densities using multivariable Cox regression models. Results Compared to PD-L1– macrophages, PD-L1+ macrophages were more likely M1-polarised than M2-polarised and located close…
Immune cell score, PD-L1 expression and prognosis in esophageal cancer
2021
Immune cell score, PD-L1 expression and prognosis in esophageal cancer