2023 Issue 7
Mechanism and effects of extramedullary hematopoiesis on anti-tumor immunity
Cancer ’s pervasive presence triggers an inflammatory response that detrimentally impacts bone marrow erythropoiesis, leading to anemia and the emergence of extramedullary hematopoiesis (EMH). In this distinct hematopoietic state, hematopoietic progenitor cells (HSPCs) are recruited to the spleen, where they undergo differentiation into myeloid-derived suppressor cells (MDSCs). Consequently, this process fosters tumor-promoting myelopoiesis and disrupts the immune system’s anti-tumor defenses. Simultaneously, tumor-induced EMH generates a surplus of erythroid progenitor cells (EPCs). Unfortunately, the majority of these EPCs not only fail to support normal hematopoiesis but also acquire pro-tumorigenic properties. Specifically, CD45-EPCs contribute to tumor progression through the secretion of artemin. Furthermore, CD45+EPCs and their derivative cells, known as erythroid-derived suppressor cells (EDMCs), significantly hinder the proliferation and immune function of CD8+ T cells. Consequently, tumor-trained EMH acts as a compensatory mechanism that undermines anti-tumor immunity.
2023 Issue 6
Neutrophils as key regulators of tumor immunity that restrict immune checkpoint blockade in liver cancer
Liver tumors characterized by intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) demonstrated moderate responses to anti-Ly6G treatment, while showing resistance to PD-1 blockade. It is worth noting that depleting neutrophils led to a substantial increase in the infiltration of CD8+ T cells in the tumor microenvironment, accompanied by a significant decrease in exhausted T cells. Moreover, a synergistic therapeutic approach combining anti-Ly6G and anti-PD-L1 agents markedly enhanced the infiltration of cytotoxic CD8+ T cells, resulting in a remarkable reduction in tumor burden.
2023 Issue 5
Nanomedicine-based combination therapies for overcoming temozolomide resistance in glioblastomas
Temozolomide (TMZ) is the first-line chemotherapeutic drug for glioblastoma (GBM) treatment which is troubled by its severe resistance developed by multiple mechanisms including reduced drug uptake, increased drug efflux, DNA damage repair, and heterogeneous tumor microenvironment. As these drug resistances involve in complicated signal networks and various compensatory mechanisms, combination therapy that targets multiple pathogenic pathways is an attractive strategy to address drug resistance and improve chemosensitivity of GBM. Currently, nanotechnology has provided new opportunities for GBM treatment through improving blood-brain barrier (BBB) permeability and GBM accumulation. Moreover, drug delivery system could be elaborately designed to load multiple therapeutics and further optimized to maximize the therapeutic efficiency of combination therapies, including combination chemotherapy, chemotherapy-gene therapy, chemo-phototherapy, and chemoimmunotherapy.
2023 Issue 4
Facing challenges with hope: universal immune cells for hematologic malignancies
As allogenic cells, universal immune cells are rarely rejected by the host immune system and always lead to transplantation tolerance. Thanks to their special immune tolerance characteristics and anti-tumor ability, universal immune cells are possible candidates for allogenic transplantation. However, the proliferation and persistence efficacy of universal immune cells warrant improvement. The combination of activated cytokines, checkpoint inhibition, CTLA-4 Ig, anti-CD52 antibodies, and TKIs may improve the clinical efficacy of universal immune cells.