RESUMO
Cancer stem cells (CSCs), being the primary contributors in tumor initiation, metastasis, and relapse, ought to have seminal roles in evasion of immune surveillance. Tumor-promoting CD4+CD25+FOXP3+ T-regulatory cells (Tregs) have been described to abolish host defense mechanisms by impeding the activities of other immune cells including effector T cells. However, whether CSCs can convert effector T cells to immune-suppressive Treg subset, and if yes, the mechanism underlying CSC-induced Treg generation, are limitedly studied. In this regard, we observed a positive correlation between breast CSC and Treg signature markers in both in-silico and immunohistochemical analyses. Mirroring the conditions during tumor initiation, low number of CSCs could successfully generate CD4+CD25+FOXP3+ Treg cells from infiltrating CD4+ T lymphocytes in a contact-independent manner. Suppressing the proliferation potential as well as IFNγ production capacity of effector T cells, these Treg cells might be inhibiting antitumor immunity, thereby hindering immune-elimination of CSCs during tumor initiation. Furthermore, unlike non-stem cancer cells (NSCCs), CSCs escaped doxorubicin-induced apoptosis, thus constituting major surviving population after three rounds of chemotherapy. These drug-survived CSCs were also able to generate CD4+CD25+FOXP3+ Treg cells. Our search for the underlying mechanism further unveiled the role of CSC-shed immune-suppressive cytokine TGFß, which was further increased by chemotherapy, in generating tumor Treg cells. In conclusion, during initiation as well as after chemotherapy, when NSCCs are not present in the tumor microenvironment, CSCs, albeit present in low numbers, generate immunosuppressive CD4+CD25+FOXP3+ Treg cells in a contact-independent manner by shedding high levels of immune-suppressive Treg-polarizing cytokine TGFß, thus escaping immune-elimination and initiating the tumor or causing tumor relapse.
RESUMO
BACKGROUND: Hydatidiform mole (HM) is characterized histologically by cystic swelling of the chorionic villi, accompanied by variable trophoblastic proliferation. The most important reason for the correct recognition of moles is that they are associated with an increased risk of persistent trophoblastic disease (invasive mole) or choriocarcinoma. AIMS AND OBJECTIVES: The aim of the study was to determine whether there is any role of p57 in differentiating partial and complete moles by immunohistochemical staining. MATERIALS AND METHODS: A prospective observational study was undertaken in which 40 cases of molar pregnancy included over a period of 2 years. Detailed clinical and family histories were obtained from each patient. Histopathological examination followed by immunohistochemical study with p57 done in each case. Ultrasonography findings and serial titers of serum beta-human chorionic gonadotropin were noted whenever necessary. RESULTS: Among the forty cases included, 25 (62%) had complete molar (CM) pregnancy, whereas the rest 15 (38%) had partial mole (PM). Both CM and PM were more pronounced in the age group of 20-25 years (44% and 60%, respectively), and among nulliparous women (68% and 70% respectively), 17 (42.5%) mothers had a prior history of abortion. In the histologically unequivocal cases of complete mole, 96% (24 of 25) did not express p57 and a single case was focal positive. In contrast, it was strongly and continuously expressed in both villous cytotrophoblast and stromal cells in all cases of PM (15 of 15). CONCLUSION: p57 immunomarker is very helpful to diagnose and differentiate complete and partial HM.
