The tumor associated antigen RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) expressed with high frequency in various cancer and trophoblast cells, inhibits growth of estrogen receptor-expressing cells and induces apoptosis. Because previous reports demonstrated RCAS1 presence only by non-quantitative immunocytochemistry methods, we decided to use a Western blotting with anti-RCAS1 monoclonal antibodies for estimation of the relative content of the tumor-associated antigen. One hundred tissue samples were assayed (neoplasms, chronic inflammatory diseases, healthy tissues, trophoblasts and placentas at term). RCAS1 was present in all neoplastic, placental and trophoblast tissue samples and its level in malignant samples was statistically significantly higher than in benign neoplasms. The amount of RCAS1 in chronic inflammations was also significantly increased in immune mediated diseases, like allergic nasal polyps and sarcoidosis. The RCAS1 protein was not revealed in healthy mucous membrane and in muscle tissues. The presented results suggest that RCAS1 might play an important role in tumor escape from host immunological surveillance and carry weight in the down regulation of the maternal immune response, thereby maintaining pregnancy.
The tumour microenvironment diversity among patients poses a challenge for conventional therapies, leading to limited efficacy. Furthermore, conventional methods are inherently associated with a negative impact on healthy tissues. Personalized immunotherapy, focused on individual tumor characteristics, has emerged as a potential solution. Neoantigens, unique antigens arising from tumour-specific mutations, play a crucial role in personalized therapy. Identifying and utilizing neoantigens through therapeutic vaccines can induce an immune response specifically against tumour cells, offering a more targeted and less toxic for healthy tissues approach to cancer treatment. The vaccines can potentially lead to tumour regression and improved outcomes. The effectiveness of this therapy is still limited due to phenomena such as immune escape. However, ongoing scientific research, technological advancements, and emerging combination therapies offer hope for the success of neoantigen-based therapeutic cancer vaccines, ushering in a new era in personalized oncology.
One of the most promising strategies in colon cancer therapy is the sensitization of cancer cells to natural proapoptotic cytokines, such as death ligands and interferons, which are able to eliminate abnormal cells. The investigation of mechanisms determining the immune escape of cancer cells revealed the presence of antiapoptotic proteins, such as cFLIP, which inhibit cell death signal transduction. Numerous studies showed that the use of different metabolic inhibitors, such as cycloheximide (CHX), reduces the cFLIP protein level, thus restoring the susceptibility to TNF-a-induced apoptosis. However, high non-specific toxicity of CHX excludes the clinical use of this substance. The current efforts are focused on identification of bioactive compounds which could safely support immunotherapy. The review presents in vitro and in vivo evidence that butyrate (Bt), fatty acid produced in colon during fermentation process and parthenolide (PN), sesquiterpene lactone isolated from Tanacetum parthenium specifically affect different cancer cells. Among described various molecular mechanisms of Bt and PN action, one reduces the level of antiapoptotic proteins. This paper clearly demonstrates that bioactive compounds, especially combined with immune cytokines could be seriously considered as an alternative for routine colon anti-cancer therapy.
Immunotherapy nowadays becomes an increasingly important topic in oncology. Immunotherapeutic strategies implemented to date focused mainly on stimulation or supplementation of function of effector cells. Past decade witnessed a tremendous progress in our understanding of mechanisms whereby tumors acquire an ability to escape host’s immune surveillance. There appeared the notion of cancer-dependent “immunosuppressive network”. An indicator of immunosuppression in tumor microenvironment is the presence of regulator T lymphocytes (Tregs) of the CD4+T subgroup. Expression of FOXP3 is directly associated with suppressive function of these cells. Other studies revealed that indoleamine 2.3-dioxygenase (IDO) induces peripheral immune tolerance to tumor antigens. In physiological conditions, IDO is indispensable in creation of a microenvironment preventing destruction of selected tissues by “hyperactive” immune system. It is currently believed that IDO-dependent increase of immune suppression enables survival and proliferation of cancer cells. Analysis of expression of FOXP3 antigens and IDO will provide an insight to the extent of “immunosuppressive network” in direct neighborhood of vulvar cancer cells and in adjacent lymphatic system. Further research focused on tumor-dependent “immunosuppressive network” is of paramount importance, as it may provide entirely new targets for therapeutic intervention, this time using low-molecular-weight compounds instead of biological factors used hitherto in immune therapies. This paper explains basic concepts of immunoedition theory and describes the role of IDO and regulatory T lymphocytes (Tregs) in the escape of cancer cells from immune surveillance.
PL
W ostatnim czasie szczególnego znaczenia w onkologii nabiera immunoterapia. Dotychczasowe strategie immunoterapeutyczne skupiały się głównie na stymulowaniu lub uzupełnianiu funkcji komórek efektorowych. W ostatnim dziesięcioleciu dokonał się ogromny postęp w zrozumieniu sposobu, w jaki guzy nowotworowe nabywają zdolność do ucieczki przed układem immunologicznym. Pojawiło się pojęcie sieci immunosupresyjnej powstającej pod wpływem raka. Wykładnikiem immunosupresji w mikrośrodowisku guzów nowotworowych jest obecność regulatorowych limfocytów T (Tregs), które należą do podgrupy komórek CD4+T. Ekspresja FOXP3 jest bezpośrednio związana z supresyjną funkcją tych komórek. W innych badaniach wykazano, że indoleamina 2,3-dioksygenaza (IDO) powoduje powstawanie obwodowej tolerancji immunologicznej wobec antygenów guza. W stanie fizjologicznym IDO jest niezbędna w tworzeniu środowiska, które ogranicza zniszczenie tkanek przez „nadaktywny” układ odpornościowy. Uważa się, że zwiększanie supresji immunologicznej przez IDO umożliwia przetrwanie i wzrost komórek rakowych. Analiza ekspresji antygenów FOXP3 oraz IDO pozwoli na zbadanie, jak duża jest „sieć immunosupresyjna” w bezpośrednim sąsiedztwie komórek raka sromu oraz w przyległym do nich układzie limfatycznym. Poszukiwanie „sieci immunosupresyjnych” wytwarzanych przez nowotwór wydaje się mieć ogromne znaczenie, ponieważ mogą dostarczyć całkiem nowych miejsc dla terapeutycznej interwencji, tym razem przy użyciu małych związków molekularnych zamiast stosowanych dotychczas (w immunoterapiach) czynników biologicznych. W poniższym artykule autorzy wyjaśniają podstawy teorii immunoedycji oraz opisują udział IDO i regulatorowych limfocytów T (Tregs) w ucieczce komórek nowotworowych spod nadzoru immunologicznego.
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