- MeSH
- Hypersensitivity diagnosis drug therapy MeSH
- Autoimmunity immunology drug effects MeSH
- Biological Therapy methods adverse effects MeSH
- Immunity, Cellular MeSH
- Immunologic Tests MeSH
- Immunotherapy MeSH
- Comorbidity MeSH
- Humans MeSH
- Interdisciplinary Communication MeSH
- Neoplasms * drug therapy immunology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
Data z recentních studií ukazují, že klasifikace imunitního systému (immunoscore) u pacientů s nádorovým onemocněním má v některých případech větší prognostický význam než TNM klasifikace. Délka přežití pacientů s určitou diagnózou se stejnou TNM klasifikační hodnotou může být značně odlišná. Metoda immunoscore kvantifikuje a detekuje jednotlivé typy imunitních buněk v nádorové tkáni pacienta, kde rovněž určuje hustotu jejich infiltrace a jejich lokalizaci. V současné době se v rámci multicentrické mezinárodní spolupráce 23 center ze 17 zemí (včetně našeho pracoviště) hodnotí immunoscore u více než 7 000 pacientů s kolorektálním karcinomem z hlediska nádorového mikroprostředí se zaměřením na prezenci imunitních buněk v nádorové tkáni a v blízkosti nádoru. Výsledky metody immunoscore se dávají do korelace s těmito parametry: 1. odpovědí pacientů na léčbu, 2. mírou progrese, prognózou jejich onemocnění a dalšími imunitními parametry. Ukazuje se, že TNM klasifikace a invazivita tumoru je statisticky závislá na imunitní reakci pacienta (existuje inverzní korelace mezi hustotou infiltrace CD 8+, CD 3+ lymfocyty a rozsahem tumoru). Vysoké hustoty T lymfocytů (CD8+, CD3+) v centru a v invazivním okraji primárního tumoru jsou spojeny s delším obdobím bezpříznakového přežívání, celkového přežívání, nižším rizikem relapsu i menší pravděpodobností vzniku metastáz. Cílem projektu je zavést immunoscore do rutinní diagnostiky.
Recent studies suggest that immune‑classification (immunoscore) in cancer patients has a prognostic value in some cases that seems to be superior to the AJCC/UICC TNM classification. The clinical outcome can vary significantly among patients with a particular diagnosis within the same TNM stage. Immunoscore methodology quantifies and detects different types of immune cells in tumor tissue, and also determines the density of their infiltration and localization at the tumor site. Currently within an international collaboration of 23 centers in 17 countries (including our department), immunoscore is being evaluated in more than 7,000 colorectal cancer patients in terms of the tumor microenvironment, focusing on the presence of immune cells both in the tumor tissue and the tumor invasive margin. Immunoscore results are assessed in correlation with: 1. patient‘s response to the treatment, 2. rate of progression, disease prognosis and other immune parameters. It appears that the TNM classification and tumor invasiveness is statistically dependent on the immune response of the patient (there is an inverse correlation between the density of the infiltration of CD 8+, CD3+ lymphocytes and the tumor stage). High densities of T-lymphocytes (CD8+, CD3+) both in the core and the invasive margin of the primary tumor are associated with longer‑term asymptomatic survival, overall survival, lower risk of relapse and reduced likelihood of metastases. The project of the international collaboration aims to introduce immunoscore in routine diagnostics. Keywords: immunoscore – TNM – VEGF – TGF‑β – CD3+ lymphocytes – CD8+ lymphocytes This project was supported by AZV CR 15-28188A, the League Against Cancer and PRVOUK-P-27//LF1/1. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 4. 8. 2015 Accepted: 13. 9. 2015
- Keywords
- CD3+ lymfocyty, CD8+ lymfocyty,
- MeSH
- CD3 Complex * metabolism MeSH
- Immunity, Cellular immunology MeSH
- CD8-Positive T-Lymphocytes * immunology MeSH
- Immunologic Surveillance MeSH
- Colorectal Neoplasms * immunology classification pathology MeSH
- Humans MeSH
- Tumor Microenvironment MeSH
- Prognosis MeSH
- Neoplasm Staging MeSH
- Lymphocytes, Tumor-Infiltrating immunology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- MeSH
- Medical Oncology * MeSH
- Humans MeSH
- Neoplasms * immunology MeSH
- Societies, Medical * MeSH
- Check Tag
- Humans MeSH
In view of the fact that insufficiency in immune response often correlates with poor prognosis, research in recent years has focused on the task of describing the precise status and function of the immune system and its possible effect on cancer patients. Although more than two thirds of treated patients respond to endocrine therapy, most patients with metastatic breast cancer develop a resistance to it. Estrogen modulates angiogenesis, partially through its effects on vascular endothelial growth factor (VEGF). It also appears that transforming growth factor-beta (TGF beta) could be another factor contributing to this resistance. TGF beta is a highly immunosuppressive factor that inhibits natural and specific immunity against tumors and stimulates the production of VEGF. The purpose of the study was to monitor immune responses in patients with hormone receptor-positive breast cancer who were resistant to hormone therapy. The examination of cellular components (CD4, CD8, HLA-DR, NK cells) and humoral immunity (IgG, IgG subclasses, IgA, IgM,). TGF beta and VEGF production were monitored with special attention, along with an analysis of the changes that occurred during the hormonal treatment. 68 patients included in the research project were implemented with routine cancer treatment with endocrine therapy. Basic parameters (the histological type and grade, the degree of expression of estrogen receptors (ER) and progesterone receptors (PR), human epidermal growth factor receptor 2 (HER2), and the proliferative marker) were established. Patients were evaluated by a cancer clinical immunologist to exclude immune disorders, allergic or autoimmune origin. TGF beta and VEGF were measured by ELISA and antitumor cellular immunity (CD4, CD8) was measured by flow cytometry. Patients who failed in the first line of hormone therapy treatment were considered as resistant to hormone therapy.Depression in cellular immunity was found especially in patients with resistance to endocrine therapy. In addition, immunoglobulin plasma levels were decreased (mainly IgG4 subtype). Most patients showed clinical symptoms of immunodeficiency (frequent infections of respiratory or urinary tract, herpetic infections). Significant increases in TGF beta and VEGF plasma were also detected.The correlation of these factors with resistance to hormonal therapy and the state of anticancer immunity could be helpful in the task of predicting resistance to hormonal therapy and could contribute to the selection of targeted immune therapy in cancer patients in the future.
- MeSH
- Immunity, Cellular MeSH
- Drug Resistance, Neoplasm * MeSH
- Adult MeSH
- Immunity, Humoral MeSH
- Middle Aged MeSH
- Humans MeSH
- Breast Neoplasms drug therapy immunology blood MeSH
- Tamoxifen therapeutic use MeSH
- Transforming Growth Factor beta blood MeSH
- Vascular Endothelial Growth Factor A blood MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Female MeSH
