Browsing by Subject "INFILTRATION"

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  • Cuesta-Mateos, Carlo; Fuentes, Patricia; Schrader, Alexandra; Juarez-Sanchez, Raquel; Loscertales, Javier; Mateu-Albero, Tamara; Vega-Piris, Lorena; Espartero-Santos, Marina; Marcos-Jimenez, Ana; Sanchez-Lopez, Blanca Andrea; Perez-Garcia, Yaiza; Jungherz, Dennis; Oberbeck, Sebastian; Wahnschaffe, Linus; Kreutzman, Anna; Andersson, Emma I.; Mustjoki, Satu; Faber, Edgar; Urzainqui, Ana; Fresno, Manuel; Stamatakis, Kostantino; Alfranca, Arantzazu; Terron, Fernando; Herling, Marco; Toribio, Maria Luisa; Munoz-Calleja, Cecilia (2020)
    T-cell prolymphocytic leukemia (T-PLL) is a poor prognostic disease with very limited options of efficient therapies. Most patients are refractory to chemotherapies and despite high response rates after alemtuzumab, virtually all patients relapse. Therefore, there is an unmet medical need for novel therapies in T-PLL. As the chemokine receptor CCR7 is a molecule expressed in a wide range of malignancies and relevant in many tumor processes, the present study addressed the biologic role of this receptor in T-PLL. Furthermore, we elucidated the mechanisms of action mediated by an anti-CCR7 monoclonal antibody (mAb) and evaluated whether its anti-tumor activity would warrant development towards clinical applications in T-PLL. Our results demonstrate that CCR7 is a prognostic biomarker for overall survival in T-PLL patients and a functional receptor involved in the migration, invasion, and survival of leukemic cells. Targeting CCR7 with a mAb inhibited ligand-mediated signaling pathways and induced tumor cell killing in primary samples. In addition, directing antibodies against CCR7 was highly effective in T-cell leukemia xenograft models. Together, these findings make CCR7 an attractive molecule for novel mAb-based therapeutic applications in T-PLL, a disease where recent drug screen efforts and studies addressing new compounds have focused on chemotherapy or small molecules.
  • Almahmoudi, Rabeia; Salem, Abdelhakim; Sievilaeinen, Meri; Sundquist, Elias; Almangush, Alhadi; Toppila-Salmi, Sanna; Paavonen, Timo; Salo, Tuula; Al-Samadi, Ahmed (2018)
    Background Oral tongue squamous cell carcinoma (SCC) is characterized by early metastasis and poor prognosis. Interleukin-17F (IL-17F) plays a protective role in many tumors. However, IL-17F expression in oral tongue SCC tissue has not been investigated. MethodsResultsImmunostaining of 83 oral tongue SCC specimens and blinded-scoring were used to map IL-17F expression, location, and distribution. Survival curves were constructed according to Kaplan-Meier method. The Cox proportional hazard model was applied for univariate and multivariate survival analyses. Mast cells are the major source of IL-17F in oral tongue SCC. In multivariate analysis, only the extracellular mast cell-derived IL-17F at the tumor invasion front was associated with better disease-specific survival in patients with all-stages and early-stages of oral tongue SCC. ConclusionExtracellular mast cell-derived IL-17F is antitumorigenic in oral tongue SCC. It separates patients with early-stage disease who are at high risk from patients who are at low risk. Furthermore, when analyzing tentative prognostic molecules, we conclude that in addition to the staining intensity, attention must be paid to the cellular source, distribution, and location of the molecule.
  • Viisanen, Tyyne; Gazali, Ahmad M.; Ihantola, Emmi-Leena; Ekman, Ilse; Näntö-Salonen, Kirsti; Veijola, Riitta; Toppari, Jorma; Knip, Mikael; Ilonen, Jorma; Kinnunen, Tuure (2019)
    The dysfunction of FOXP3-positive regulatory T cells (Tregs) plays a key role in the pathogenesis of autoimmune diseases, including type 1 diabetes (T1D). However, previous studies analyzing the peripheral blood Treg compartment in patients with T1D have yielded partially conflicting results. Moreover, the phenotypic complexity of peripheral blood Tregs during the development of human T1D has not been comprehensively analyzed. Here, we used multi-color flow cytometry to analyze the frequency of distinct Treg subsets in blood samples from a large cohort comprising of 74 children with newly diagnosed T1D, 76 autoantibody-positive children at-risk for T1D and 180 age- and HLA-matched control children. The frequency of CD4+CD25+CD127lowFOXP3+ Tregs was higher in children with T1D compared to control children, and this change was attributable to a higher proportion of naive Tregs in these subjects. Further longitudinal analyses demonstrated that the increase in Treg frequency correlated with disease onset. The frequencies of the minor subsets of CD25+FOXP3low memory Tregs as well as CD25lowCD127lowFOXP3+ Tregs were also increased in children with T1D. Moreover, the ratio of CCR6-CXCR3+ and CCR6+CXCR3- memory Tregs was altered and the frequency of proliferating Ki67-positive and IFN-gamma producing memory Tregs was decreased in children with T1D. The frequency of CXCR5+FOXP3+ circulating follicular T regulatory cells was not altered in children with T1D. Importantly, none of the alterations observed in children with T1D were observed in autoantibody-positive at-risk children. In conclusion, our study reveals multiple alterations in the peripheral blood Treg compartment at the diagnosis of T1D that appear not to be features of early islet autoimmunity.
  • Almangush, Alhadi; Mäkitie, Antti A.; Mäkinen, Laura K.; Kauppila, Joonas H.; Pukkila, Matti; Hagström, Jaana; Laranne, Jussi; Soini, Ylermi; Kowalski, Luiz Paulo; Grenman, Reidar; Haglund, Caj; Coletta, Ricardo D.; Salo, Tuula; Leivo, Ilmo (2018)
    One of the main changes in the 8th edition of the American Joint Committee on Cancer (AJCC) for staging of oral cancer is the inclusion of depth of invasion (DOI) in the T category. However, cancers in different oral subsites have variable behavior, with oral tongue squamous cell carcinoma (OTSCC) being the most aggressive one even at early stage. Thus, it is necessary to evaluate the performance of this new T category in homogenous cohort of early OTSCC. Therefore, we analyzed a large cohort of patients with a small (ae4 cm) OTSCC to demonstrate the differences in T stage between the AJCC 7th and 8th editions. A total of 311 early-stage cases (AJCC 7th) of OTSCC were analyzed. We used 5 mm and 10 mm DOI for upstaging from T1 to T2 and from T2 to T3 respectively, as in the AJCC 8th. We further reclassified the cases according to our own proposal suggesting 2 mm to upstage to T2 and 4 mm to upstage to T3. According to AJCC 7th, there were no significant differences in the survival analysis. When we applied the 8th edition, many cases were upstaged to T3 and thus associated with worse disease-specific survival (HR 2.37, 95% CI 1.12-4.99) and disease-free survival (HR 2.12, 95% CI 1.09-4.08). Based on our proposal, T3 cases were associated with even worse disease-specific survival (HR 4.19, 95% CI 2.27-7.74). The 8th edition provides better survival prediction for OTSCC than the 7th and can be further optimized by lowering the DOI cutoffs.
  • Ålgars, Annika; Kemppinen, Lotta; Fair-Mäkelä, Ruth; Mustonen, Harri; Haglund, Caj; Jalkanen, Sirpa (2021)
    Simple Summary Tumor-associated macrophages can either promote or prevent cancer growth depending on factors such as macrophage polarization status, tumor type, and disease stage. Macrophages and vessels interact with each other, and the number of lymphatic vessels also affects cancer survival. CLEVER-1 is a protein expressed both on immunosuppressive M2 macrophages and lymphatic vessels. The aim of this study was to validate our previous results regarding the prognostic role of CLEVER-1(+) macrophages, CD68(+) macrophages, and CLEVER-1(+) lymphatic vessels in stage I-IV colorectal cancer. The results indicate that the prognostic role of tumor-associated macrophages and lymphatic vessels changes during disease progression. The findings resemble our earlier results, but are not completely equal, which may be due to the different types of tumor samples used in the two studies (whole section vs. tissue microarray). Macrophages, which are key players in the tumor microenvironment and affect the prognosis of many cancers, interact with lymphatic vessels in tumor tissue. However, the prognostic role of tumor-associated macrophages (TAM) and lymphatic vessels in human colorectal cancer (CRC) remains controversial. We investigated the prognostic role of CD68(+) and CLEVER-1(+) (common lymphatic endothelial and vascular endothelial receptor 1) TAMs in addition to CLEVER-1(+) lymphatic vessels in 498 stage I-IV CRC patients. The molecular markers were detected by immunohistochemical (IHC) analysis. The results showed that, in early stage I CRC and in young patients (age below median,
  • Edin, Sofia; Kaprio, Tuomas; Hagström, Jaana; Larsson, Pär; Mustonen, Harri; Böckelman, Camilla; Strigård, Karin; Gunnarsson, Ulf; Haglund, Caj; Palmqvist, Richard (2019)
    The anti-tumour immune response is critical to patient prognosis in colorectal cancer (CRC). The aim of this study was to investigate infiltration of B lymphocytes into CRC tumours, and their clinical relevance, prognostic value and relation to other immune cell subsets. We used multiplexed immunohistochemistry and multispectral imaging to assay the amount of infiltrating CD20(+) B lymphocytes along with infiltration of CD8(+) cytotoxic T cells, FOXP3(+) T regulatory cells, CD68(+) macrophages and CD66b(+) neutrophils, in 316 archival CRC tissue specimens. A higher density of infiltrating CD20(+) B lymphocytes was associated with tumours of the right colon (P = 0.025) and of lower stages (P = 0.009). Furthermore, patients whose tumours were highly infiltrated by CD20(+) B lymphocytes had a significantly improved disease-specific survival (HR = 0.45, 95% CI 0.28-0.73, P = 0.001), which remained significant in multivariable analysis. CD20(+) B lymphocytes were highly and positively associated with CD8(+) T lymphocytes (P <0.001), and part of the prognostic role was found to be a cooperative effect between these lymphocyte subsets. Our results support a favourable prognostic value of tumour-infiltrating CD20(+) B lymphocytes in CRC. Furthermore, a cooperative prognostic effect between CD20(+) B lymphocytes and CD8(+) T lymphocytes is suggested.
  • Kilpio, Olga; Härkki, Päivi S. M.; Mentula, Maarit J.; Jokela, Ritva M.; Pakarinen, Paivi I. (2017)
    Objective: In laparoscopic adnexal surgery the conventional method of removing a mass from the abdominal cavity in Finland is through a 10-mm-wide lateral abdominal port. The larger the lateral trocar, the greater the risk of pain, complications and delayed recovery. Here, we assumed that adnexal mass removal through a 10-mm umbilical port together with 5-mm side trocars would decrease the postoperative need of analgesics when compared with removal through a 10-mm lateral abdominal port. Study design: Women scheduled for laparoscopic surgery of a benign adnexal mass were invited to participate. The participants were randomized into two groups: removal via the transumbilical (TO) (n = 21) or lateral transabdominal (TA) (n= 21) route. General anesthesia and use of local anesthetics were standardized. The amount of postoperative opioid (oxycodone) and visual analog scale (VAS) scores for pain were the primary outcome measures. Secondary outcome measures were nausea/vomiting (VAS evaluation), time to discharge, peri- and postoperative complications, surgeons' opinions of the alternative methods and patients' satisfaction, evaluated via a questionnaire sent six months postoperatively. Results: There were no significant differences in the use of opioids or median pain-VAS scores between the groups during the first 24 h postoperatively. However, in the TU group the amount of women with very low pain-VAS scores (0-1) during the whole 12-h follow-up time was significantly greater than in the TA group (4 vs. 0 women p=0.04). The amounts of nausea and vomiting, and median times to discharge were similar in both groups. There were no major complications. Conclusions: Both transumbilical and transabdominal routes of abdominal mass removal during laparoscopy were feasible and safe. However, the transumbilical route resulted in more women with very low pain-VAS scores. (C) 2017 Elsevier B.V. All rights reserved.