Tumor Immunology

Cancer immunotherapy is a rapidly advancing medical therapy that takes advantage of the immune system to contain or eliminate cancer cells. Currently, immunotherapies have been incorporated into treatment regimens for different types of cancer. Various therapeutic approaches exist, including using cytokines, vaccines, oncolytic viruses, T-cell manipulation or cellular adoptive immunotherapy, or antibodies to immune checkpoint molecules. These therapies provide new options for advanced cancers, including melanoma, renal cell carcinoma, prostate adenocarcinoma, lung cancer, urothelial carcinoma, Hodgkin lymphoma, and refractory B-cell ALL. With the immune system involved, these agents carry serious and potentially fulminant adverse effects and toxicities.

Targeted therapy exerts antineoplastic activity against cancer cells by interfering with unique properties found in tumors or malignancies. The types of drugs can be small molecules, which are able to enter cells, or monoclonal antibodies, which have targets outside of or on the surface of cells. Among the areas in malignant cells that are blocked or inhibited by targeted therapy are signal pathways (as seen in protein kinase inhibitors), which lead to decreased proliferation and subsequent tumor cell apoptosis. Other means of reducing cancer cells is by eliminating the capacity for DNA repair (seen in poly(ADP-ribose) polymerase inhibitors), blocking the ligand-receptor binding (growth factor inhibitors), and increasing immune activity against the neoplasm (immunotherapies). These agents are used in multiple types of cancer and in combination with traditional chemotherapeutic agents.

Chronic lymphocytic leukemia (CLL) is a hematologic malignancy characterized by excess production of monoclonal B lymphocytes in the peripheral blood. When the involvement is primarily nodal, the condition is called small lymphocytic lymphoma (SLL). The disease usually presents in older adults, with a median age of 70 years. Clinical presentation is often asymptomatic and diagnosis is made when abnormal lymphocytosis is seen on laboratory testing. Cytopenias can also be seen. The B cells are functionally incompetent lymphocytes and thus may result in recurrent infections. Treatment can vary from watchful waiting for early stages to chemotherapy for later stages. Median survival is around 10 years.

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by the uncontrolled proliferation of myeloid precursor cells. Seen predominantly in older adults, AML includes an accumulation of myeloblasts and a replacement of normal marrow by malignant cells, which leads to impaired hematopoiesis. Clinical presentation consisting of fatigue, bleeding, fever, and infection is related to anemia, thrombocytopenia, and a lack of functional WBCs. The onset of symptoms takes days to weeks. Additional findings in AML may include gingival hypertrophy and skin infiltration (leukemia cutis). Diagnosis is via peripheral blood smear and bone-marrow biopsy examination (shows myeloblasts). The precursor cells contain Auer rods. Immunophenotyping, histochemistry, and genetic analysis all aid in identifying and guiding the treatment of AML. Management is chemotherapy administered in phases (induction, consolidation, and maintenance) based on subtypes. Prognosis varies according to the age of onset and type of leukemia.

Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Osteoclastic activity results in bone resorption, bone pain, pathologic fractures, and metabolic disturbances. Excessive secretion of antibodies results in proteinuria and associated kidney damage as well as production and tissue deposition of amyloid fibrils. Metabolic disturbances combined with tissue amyloid deposition cause end-organ damage. Diagnosis is established by plasma electrophoresis and bone marrow biopsy. Treatments to slow down the disease progression are available; however, there is no cure for MM. The median survival is approximately 3 years.

Hodgkin lymphoma (HL) is a malignancy of B lymphocytes originating in the lymph nodes. The pathognomonic histologic finding of HL is a Hodgkin/Reed-Sternberg (HRS) cell (giant multinucleated B cells with eosinophilic inclusions). The disease presents most commonly with lymphadenopathy (neck most commonly involved), night sweats, weight loss, fever, and at times, splenomegaly and hepatomegaly. Diagnostic testing includes lymph node histologic analysis showing HRS cells, blood tests, and CT and PET scanning. HL is managed with chemotherapy and radiotherapy. The prognosis has improved significantly with the advent of chemotherapeutic regimens.