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Cancer Immunology, Hematology, and Etiology Research

Conceptual image Bacteria on blurred background 3D rendering.

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Research funded in the area of cancer immunology and hematology aims to characterize basic biological mechanisms underpinning anti-tumor immune responses, with an emphasis on immune regulation of the development and spread of tumors and approaches to improve immune targeting and destruction of cancer cells. It also includes research into the molecular bases of hematologic malignancies, including leukemia, lymphoma, multiple myeloma, chronic and acute myeloid leukemia, hematologic cancer stem cells, as well as studies of graft versus host (GVH) disease and the graft versus leukemia (GVL) effect.

Cancer etiology research investigates biological agents and host predisposing states that are possible etiological factors or cofactors in cancer. Biological agents are primarily viruses and bacteria but also include other multicellular pathogens involved in the initiation, promotion, or resistance of human cancers. Host predisposing states are those that initiate or promote cancer, such as obesity, diet, comorbid conditions, and aging. 

Research in this area is supported and directed by the Cancer Immunology, Hematology, and Etiology Branch (CIHEB).

Anti-tumor Immunity (Innate and Adaptive)

Achieving a deeper understanding of how the innate and adaptive immune systems regulate anti-tumor immune responses will inform future cancer immunotherapies.

Key research areas include:

  • Innate immune cell populations that initiate or carry out anti-tumor immune responses (e.g., macrophages, dendritic cells (DCs), neutrophils, mast cells, natural killer (NK) cells, NKT cells, intra-epithelial lymphocytes (IELs), and gamma delta T cells)
  • Adaptive immune cell populations that initiate or carry out immune responses
  • Regulatory interactions among innate and adaptive immune cell populations
  • Biological effects of immunotherapies on innate and adaptive immune cell populations
  • Regulation of adaptive immune cell responses to cancer and how these can be optimized to achieve tumor eradication or stasis

Emerging research areas include engineering innate and adaptive immune cells to target and kill tumors and enhance immunotherapy approaches, multi-modal approaches to interrogate the immune microenvironment of solid tumors, the roles of circulating and tissue-specific immune cell populations in immune surveillance of cancer and in tumor rejection, understanding the role of age and sex in anti-tumor immunity, and determining how the microbiome influences anti-tumor immune responses.

B and T Lymphoid Malignancies

Understanding the molecular bases of lymphoid malignancies will uncover novel molecular targets that these tumors rely on for their growth and survival.

Key research areas include:

  • Aberrant B cell receptor or T cell receptor signaling
  • Increased expression of anti-apoptotic pathways
  • Loss of tumor suppressor pathways
  • Loss of genome stability (chromosomal translocations and mutation)
  • Induction of activation pathways (e.g., Notch signaling) 

Emerging areas relevant to this research include understanding the mechanisms mediating genomic instability and leukemia heterogeneity, the development of models to predict disease course, uncovering the mechanisms of therapy resistance and recurrent disease, signaling pathways regulating leukemia stem cells, and extracellular factors that promote leukemias, including components of the bone marrow, lymph node, and germinal center microenvironments. 

Hematopoiesis and Myeloid Malignancies (Acute and Chronic)

Myeloid malignancies are complex diseases with considerable phenotypic and genotypic heterogeneity. Understanding the basic biology of hematopoiesis to myeloid cancers is important to determine mechanisms that drive these types of cancers. 

Key research areas include:

  • Basic cell biology of hematopoiesis related to leukemogenesis
  • Growth and survival mechanisms of leukemic cells
  • Molecular drivers of leukemogenesis
  • Mutations that play a role in myeloid malignancies

Emerging areas relevant to this research include understanding the biology of aging, clonal hematopoiesis and mechanisms of malignant transformation, mechanisms of therapy resistance, and the role of the microenvironment in leukemogenesis.

Viral Carcinogenesis

Evidence suggests that viruses and other microbes contribute to the etiology of as much as 20 percent of human cancers. Major goals of studies supported in this area are to identify pathways by which viral pathogens transform human cells and to design strategies to interfere with these processes. 

Key research areas include:

  • Biological role of viruses in cancer 
  • Development of experimental models to understand viral carcinogenesis
  • Immune responses to oncoviruses (e.g., papillomaviruses, herpesviruses, hepatitis viruses, etc.)
  • Understanding the complex relationship between HIV infection and the emergence of both AIDS-defining and non-AIDS-defining cancers

Emerging areas relevant to this research include understanding mechanisms of co-infection and cancer (e.g., interactions and potentiating factors) and the role of the tumor microenvironment in the development of cancer in individuals with HIV or AIDS. 

Bacterial Carcinogenesis and the Role of the Microbiome

Increasing evidence indicates that the human microbiome, particularly bacteria in the gut, plays an important role in the initiation and progression of cancer. Research funded in this area seeks to determine the role and mechanism of bacterial carcinogens in cancer and their interactions with other etiologic agents.

Key research areas include:

  • The etiological role that changes in the microbiome have on intestinal epithelial cells and the immune system during carcinogenesis
  • Isolation and characterization of microbial agents that may cause or promote tumorigenesis
  • Identification of molecular interactions between host cells and microbiota
  • Oncogenic host responses to microbial agents and their secreted products 
  • Development of tools and preclinical models to determine molecular mechanisms of microbial carcinogenesis

Emerging areas relevant to this research include linking the microbiome metabolic output to cancer and targeting this output for clinical translation (e.g., prevention, early detection, therapy), understanding how the microbiome regulates host cell epigenetics during carcinogenesis, using systems biology to understand the role of the microbiome in cancer, understanding how glycan-mediated interactions between host and microbes influence cancer initiation, progression, and treatment. 

Host Predisposing States

Host predisposing states include obesity, diet, comorbid conditions, and aging that initiate or promote cancer. A critical aspect of understanding the complex origins of cancer is to identify those factors or conditions that either accelerate or slow cancer progression.

Key research areas include:

  • The role of developmental and life stages in the susceptibility to etiological factors
  • The effect of diet or dietary components on the microbiome and carcinogenesis
  • Microbial modulation of host genes and factors that affect metabolism
  • The role of comorbidities as etiological factors in cancer (e.g., aging, metabolic syndrome, diabetes, chronic obstructive pulmonary disease (COPD), and liver disease)

Emerging areas relevant to this research include investigating the role of obesity-induced metabolic dysregulation in cancer, including the effects on tumor cell intrinsic and extrinsic factors, the role of liver disease and the development or progression of hepatocellular carcinoma, and understanding mechanisms of aging that contribute to cancer initiation.

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