INFLUENCE OF IMMUNE STATUS OF THE IMMUNE DEFICIENT MICE ON THE METASTATIC PHENOTYPES OF THE HETEROGENEOUS CLONAL SUBLINES OF HUMAN LUNG GIANT CELL CARCINOMA

By using cell cloning technique, 4 sublines (A,C,D,E) were isolated from a cell line of human lung giant cell carcinoma (PLA-801). After subcutaneous inoculation in T-cell deficient BALB/c nude mice, the incidence of tumor growth and spontaneous metastasis were the highest in subline D, moderate in sublines A and E, and lowest in subline C. Tumor cells of subline C also showed similar low tumorigenicity in another T-cell deficient 615/ PB1 nude mice.However, in 615/PB1 beige nude mice with con-genitally combined immune-deficiency in both T and NK cell activity, tumor cells of the rarely metastatic subline C do produce significantly high frequency of tumor growth and spontaneous metastasis.Morphological studies (light microscope, electron microscope and immunohistochemistry) showed rich microfilaments and Vimentin positive in the cytoplasm of metastatic tumor cells. This may imply a possibility that tumor cells differentiate towards the direction favourable to spreading and metastasis.

Heterogeneity of the tumor immune microenvironment and clinical interventions

The tumor immune microenvironment(TIME)is broadly composed of various immune cells,and its heterogeneity is characterized by both immune cells and stromal cells.During the course of tumor formation and progression and anti-tumor treatment,the composition of the TIME becomes heterogeneous.Such immunological heterogeneity is not only present between populations but also exists on temporal and spatial scales.Owing to the existence of TIME,clinical outcomes can differ when a similar treatment strategy is provided to patients.Therefore,a comprehensive assessment of TIME heterogeneity is essential for developing precise and effective therapies.Facilitated by advanced technologies,it is possible to understand the complexity and diversity of the TIME and its influence on therapy responses.In this review,we discuss the potential reasons for TIME heterogeneity and the current approaches used to explore it.We also summarize clinical intervention strategies based on associated mechanisms or targets to control immunological heterogeneity.

The Oncogenesis of Glial Cells in Diffuse Gliomas and Clinical Opportunities

Glioma is the most common and lethal intrinsic primary tumor of the brain.Its controversial origins may contribute to its heterogeneity,creating challenges and difficulties in the development of therapies.Among the components constituting tumors,glioma stem cells are highly plastic subpopulations that are thought to be the site of tumor initiation.Neural stem cells/progenitor cells and oligodendrocyte progenitor cells are possible lineage groups populating the bulk of the tumor,in which gene mutations related to cell-cycle or metabolic enzymes dramatically affect this transformation.Novel approaches have revealed the tumor-promoting properties of distinct tumor cell states,glial,neural,and immune cell populations in the tumor microenvironment.Communication between tumor cells and other normal cells manipulate tumor progression and influence sensitivity to therapy.Here,we discuss the heterogeneity and relevant functions of tumor cell state,microglia,monocyte-derived macrophages,and neurons in glioma,highlighting their bilateral effects on tumors.Finally,we describe potential therapeutic approaches and targets beyond standard treatments.