For example, approved therapies such as anthracyclines and bortezomib induce immunogenic death of tumor cells via exposure of heat-shock proteins47,48. to prevent or treat cancer. Distinct aspects of hematologic malignancies Artemisinin as relevant to immune-modulation In recent years, immunomodulatory Artemisinin approaches have attracted much attention in solid tumors. In this review, we discuss key aspects of the emerging field of immunomodulation, as they apply to hematologic malignancies. Hematologic malignancies are a diverse group of at least 30 different tumor types, each with distinct biology, pathogenesis and clinical behavior. When considering the cross-talk between malignancy and the immune system, it is useful to classify hematologic tumors based on cell of origin, into those that involve multi-potent stem cells (such as acute leukemias), and those (such as lymphoma, myeloma) wherein the target of transformation is a committed lymphoid or myeloid progenitor/progeny. A practical implication of this distinction is that the former are often characterized by severe cytopenias including normal immune cells, and therefore immune-therapeutic strategies need to first restore normal hematopoiesis or adoptively transfer immune effector cells. Some aspects of the biology of hematologic malignancies deserve distinct considerations (Table 1). Several hematologic malignancies are characterized by systemic involvement of secondary lymphoid tissues. In some settings, the tumor cells may share the developmental niche with normal immune cells leading to immune-paresis. This is commonly exemplified in B cell malignancies such as myeloma and chronic lymphocytic leukemia with a reduction in normal B/plasma cells and consequently hypogammaglobulinemia. In some tumors, cross-talk with normal immune cells may impact tumor growth and survival more directly as it resembles physiologic cell-cell interactions. An example of the latter may be interactions between dendritic cells and tumor cells, or between certain T cell subsets such as T-follicular helper (TFH) cells and tumor cells1,2. Such interactions may also impact immune therapies. For example, TFH cells are characterized by the expression of programmed-death-1 (PD-1), which is also targeted in immune checkpoint blockade. Table 1 Some distinct considerations for immune-modulation in hematologic malignancies thead th valign=”top” align=”left” rowspan=”1″ colspan=”1″ Property of hematologic malignancies /th th valign=”top” align=”left” rowspan=”1″ colspan=”1″ Implications /th /thead Common involvement of secondary lymphoid tissueDifferences in chemokine requirement for T cell infiltration into tumor tissueShared niche with normal lymphoid cells (lymphoid tumors)Immune paresisHematopoietic stem cell involvement (e.g. acute leukemia)CytopeniasRole of physiologic interactions with other immune cells due Artemisinin to immune cell of origine.g. TFH-B cell interactions may promote tumor growthBone marrow involvementMarrow as a distinct immune tissueSusceptible to both adaptive and innate lymphocytesTargets for both innate and adaptive immunityPrecursor states (e.g. MGUS) unresectableModels to study immune-surveillanceLess mutational complexity (compared to most solid tumors)? more amenable to personalized immunotherapy Open in a separate window Bone marrow involvement is a common feature of hematologic malignancies. Bone marrow represents a distinct immunologic tissue and therefore properties of marrow-resident immune cells are likely to impact Artemisinin immune therapies against these tumors3. From a genetic perspective, hematologic malignancies carry fewer mutations and exhibit lower degree of intraclonal diversity compared to many solid tumors. These considerations mCANP make these tumors attractive targets for therapies targeting selected driver mutations, but the lower mutation load may in principle also translate to fewer neo-antigens and therefore fewer targets for adaptive immune responses. Nevertheless, most hematologic malignancies are highly susceptible to lysis by both innate and adaptive immune cells. Finally, several hematologic malignancies also represent important models to understand immune-surveillance of human tumors as they are characterized by well-defined precursor states amenable to prospective analysis and the ability to isolate individual tumor/precursor cells and surrounding immune cells..