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The effect of COVID-19 on cancer immunotherapy and cancer care

Summary of key facts SARS-CoV-2 was initially detected in December 2019 and is an enveloped, single-stranded RNA virus causing an extremely contagious severe respiratory illness with a high rate of mortality. Whole genome sequencing confirmed COVID-19 to be 79.6% similar to SARS and MERS, which belong to β-CoV genera, one of four identified coronavirus genera. SARS-CoV-2 is a respiratory virus and spreads mainly through person-to-person contact…

The clinical application of immuno-therapeutics

Summary of key facts Immuno-oncology (IO) is one of the fastest-growing therapeutic areas within oncology. IO agents work indirectly via the host’s adaptive and innate immune systems to recognize and eradicate tumor cells. Current FDA-approved classes of IO agents include immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR) T-cell therapy, bispecific T-cell engager (BiTE) antibody therapy, cancer vaccine therapy, and oncolytic virus therapy. Cancer immunotherapy has…

The microbiome and cancer immunotherapy

Summary of key facts The human microbiota is composed of bacteria, viruses, fungi, yeast, protozoa, and archaea. Because of its commensal relationship with the host, it is identified as a functioning organ system. The gut microbiota has been shown to have a critical role in immunotherapy outcomes. Colonies of the microbiota are found on the surfaces of the digestive tract, respiratory system, urogenital tracts, and skin.…

The major clinical components of cancer immunotherapy (modulating cell-mediated immune mechanisms)

Summary of key facts Immune checkpoints are molecular pathways that blunt the antitumor immune response via limiting the creation of cytotoxic T cells and triggering exhaustion of tumor-reactive immune cells. Immune checkpoint inhibitors, especially those targeting the PD-1/PD-L1 pathway, are used to treat patients with a wide range of cancers. Adoptive transfer of TILs can result in clinical responses in patients with metastatic melanoma. T cells…

Vaccines and active immunization against cancer

Summary of key facts Cancer vaccines represent a promising strategy to activate immunity in cold tumors. The complexity and heterogeneity of human tumors remains a challenge to developing cancer vaccines. Sipuleucel-T is the first therapeutic vaccine approved for cancer. Cancer vaccines targeting unmutated tumor-associated antigens (TAAs) have had poor results in the clinic. Neoantigens that arise from tumor-specific mutations are immunogenic, drive antitumor immune responses, and…

Cancer—avoiding immune detection

Summary of key facts The natural history of a human malignancy and its relationship to the host immune system has been described as comprising the “three Es”: elimination, equilibrium, and escape. In order to progress, the tumor needs to escape immune control by the cell destructive capacities of the CD8 + T cells of the adaptive immune system and of the NK cells of the innate…

The essential elements of adaptive immunity and their relevance to cancer immunology

Summary of key facts Receptors of adaptive immune cells and the ensuing signaling networks are exquisitely specific and sensitive to new or altered antigens and thus poised to respond to tumors. The capacity of adaptive immune cells to traffic to sites of inflammation is programmed during initial priming and allows them to seek and destroy metastatic deposits throughout the body. The ability to form self-renewing memory…

Tumor immune surveillance

Summary of key facts The concept of tumor immunosurveillance can be traced back to the early 1900s in association with observations that a potentially overwhelming frequency of carcinomas must be repressed by the immune system. The cancer immunosurveillance hypothesis was formally proposed in 1970 by Burnet and Thomas, , describing the immune contribution to tumor control as an “evolutionary necessity” given the lifetime accumulation of genetic…

Tumor antigenicity and cancer as non-self

Summary of key facts Professor Paul Ehrlich is credited with introducing the concept of cancers as non-self and proposing the concept of tumor immune surveillance in 1909. Evidence for tumor immunity was suggested by early animal tumor transplantation experiments carried out in nonhomogeneous mouse strains. The development of congenic inbred murine strains was an essential contribution that enabled the study of human tumor immunogenicity. TSTAs (tumor…

Cancer and the science of innate immunity

Summary of key facts The innate immune system is the host’s first line of immune defense against challenges of the environment. The innate immune system response is a nonrestricted, rapid response. Innate immunity is required for the establishment of adaptive immunity, or immune memory. Cellular components comprising the innate system include monocytes, macrophages, dendritic cells, and granulocytic cell types such as neutrophils, mast cells, eosinophils, and…

The role of the complement system in cancer etiology and management

Summary of key facts The complement system is a key component of the innate immune system, responsible for facilitating immune defense mechanisms, regulating inflammation, and maintaining tissue homeostasis. The complement system is a proteolytic cascade, comprising more than 50 highly regulated soluble proteins and membrane-bound receptors. The cascade is initiated by recognition of pathogen-associated patterns (PAMPs), damage-associated molecular patterns (DAMPs), and binding to immune complexes and…

The chemistry, structure, and function of immunoglobulins

Summary of key facts Immunoglobulins (Igs) are the soluble mediators of antigen recognition. An Ig that is capable of specifically binding an antigen is termed an antibody . Immunoglobulins range in molecular weight from 150 kD to 900 kD and are built from tetrameric units consisting of two heavy (H) chains and two light (L) chains, each chain containing one variable (V) domain and one or…

Development and structure of the lymphoid system

Summary of key facts The lymphatic system is a complex, blind-ended vascular tree distinct and separate from the blood circulatory system. Lymphatics facilitate tissue fluid homeostasis, nutrient uptake, and immune functions. Lymphatic vessels and lymphatic endothelial cells have unique features promoting uptake and transport back to the blood circulation. Lymphatic endothelial cell specification and differentiation are promoted by specific molecular programs. Heterogeneity and plasticity of lymphatic…

Brain Metastasis from Nasopharyngeal Carcinoma

Introduction Epidemiology and Etiology Nasopharyngeal carcinoma (NPC) has a distinct geographic and ethnic distribution, which is a result of a multifactorial etiology. NPC is rather rare in many parts of the world such as North America, but it is considered endemic in certain parts of Asia, particularly in southern China, Southeast Asia, the Arctic, North Africa, and the Middle East ( ; ; ). Migrant epidemiologic…

Brain Metastasis of Colorectal Cancer: Microenvironment and Molecular Mechanism

Introduction Colorectal carcinoma (CRC) is the third most commonly diagnosed cancer in males and the second most common in females worldwide. The main causes of failure for treatments are local recurrence and distant metastases, especially when vital organs such as liver and lung are involved through hematogenous dissemination. Brain metastasis is a much less common but more fatal condition and is usually considered as the late-stage…

Gastrointestinal Cancer and Brain Metastasis Outcomes and Management

Introduction The most common adult intracranial neoplasms are metastatic brain tumors. Metastatic tumors account for approximately 20–40% of all brain tumors and outnumber primary brain tumors 10 to 1 ( ). Two hundred thousand new cases of metastatic brain tumors are estimated to occur in the United States annually, although the exact incidence of brain metastasis is unknown ( ). The majority of epidemiologic studies underestimate…

Brain Metastasis from Renal Carcinoma: Locoregional and Systemic Treatments

Introduction Kidney cancer is among the 10 most common cancers in Western communities and accounts for almost 3% of worldwide adult malignancies. Each year worldwide, around 270 000 cases of kidney cancer are diagnosed and 116 000 people die from the disease. The incidence per 100 000 people of kidney cancer varies geographically: rates of kidney cancer are highest in Europe, North America, and Australia but are low in…

Brain Metastases from Esophageal Cancer in the Presence of HER-2 Overexpression

Introduction The standard approach to locally advanced esophageal carcinoma has evolved in recent years and currently involves the use of a multimodality approach with the use of concurrent chemotherapy and radiation followed by esophagectomy. Although the treatment goal is to cure the disease, recurrence rates are high and usually involve the liver, abdomen, lungs, and bone ( ). In a study by 65% of the relapses…

Melanoma Progression in the Brain: Role of Pericytes, the Basal Lamina, and Endothelial Cells in Tumor Vascularization

Introduction Melanoma is a malignancy that originates primarily in the skin ( ), although melanomas can also arise from melanocytes in other pigmented tissues such as the uvea of the eye. Although there have been many improvements in the diagnosis, excision, and treatment of primary melanomas, the lethality of these tumors stems from their aggressive metastasis to secondary sites such as brain, bone, and lung (…

Brain Metastases in Melanoma Patients: Treatment with Adjuvant Postoperative Whole-Brain Radiotherapy

Introduction Incidence of Melanoma Brain Metastases Brain metastases (BMs) of melanoma are associated with a relatively poor prognosis and can affect quality of life. Unfortunately, BMs are a common event in metastatic melanoma. Symptomatic BMs represent the initial site of metastatic spread in 20% but may occur at any time during the course of the disease ( ). Autopsy data have shown that up to 75%…