Mechanisms of Immune Tolerance in Leukemia and Lymphoma

Abstract

The mechanisms through which immune responses are generated against solid cancers are well-characterized, and knowledge of the immune evasion pathways exploited by these malignancies has grown considerably. However, for hematological cancers, which develop and disseminate quite differently than solid tumors, the pathways which regulate immune activation or tolerance are less clear. Growing evidence suggests that, while a number of immune escape pathways are shared between hematological and solid malignancies, there are several unique pathways exploited by leukemia and lymphoma. Below, we discuss immune evasion mechanisms in leukemia and lymphoma, highlighting key differences from solid tumors. A more complete characterization of the mechanisms of immune tolerance in hematological malignancies is critical to inform the development of future immunotherapy approaches.

Sex ratio among childhood cancers by single year of age

“…22 Such differences contribute to sex variation in immune response and tumor surveillance. There are mechanistic differences between solid and hematologic cancers in evading immune surveillance, 38 but whether these mechanisms differ by sex is unknown. The immune-related biologic mechanisms underlying sex differences in childhood cancer incidence may be particularly relevant for hematologic malignancies as these arise in cellular components of the immune system.…”

B7-Positive and B7-Negative Acute Myeloid Leukemias Display Distinct T Cell Maturation Profiles, Immune Checkpoint Receptor Expression, and European Leukemia Net Risk Profiles

“…Thus, these non-inflamed, low immunogenic AML types are likely less capable of priming T cells and mounting antileukemia immune responses. Therefore, B7-negative AML should be approached differently by adoptive cell transfer (chimeric antigen receptor T cells), leukemia peptide vaccines, or strategies that augment tumor cell immunogenicity and convert "non-inflamed" LMEs to inflammatory ones, such as hypomethylating agents (9,15).…”

“…Recent research revealed that immune profiles are identifiable in human AML and hold prognostic and therapeutic relevance (9,14). The AML immune response shares numerous traits with solid cancers (15) and offers various opportunities for immunotherapy (9). However, given its origin within an immune-privileged, regulatory T cell (Treg)abundant bone marrow (BM) niche (16), its low mutational load (11), deficient antigen presentation (17)(18)(19)(20), aggressive growth, and bloodstream dissemination (21,22), AML was regarded as a poorly immunogenic tumor with a rather "immune-desert" leukemia microenvironment (LME) phenotype (9), in which immunoediting is either absent or a rather late event (23).…”

Discovery and application of immune biomarkers for hematological malignancies

“…In light of their origin from primary and secondary lymphoid tissues, haematological malignancies might be characterised by distinctive mechanisms of immune evasion compared with solid tumours [26]. In principle, haematological malignancies are poorly immunogenic and highly immune suppressive.…”