The Aging Immune System
Constantin A. Bona, Francisco A. Bonilla in Textbook of Immunology, 2019
Concurrent with the decline in specific anti-microbial humoral immunity, the amount of self-specific antibodies increases. These are commonly of the “natural autoantibody” type (see Chapters 5 and 12), i.e., low-affinity polyspecific IgM. The majority of these arise from CD5+ B cells, whose specificity repertoire is heavily skewed toward natural autoantibodies. The percentage of CD5+ B cells increases with age. Chronic lymphocytic leukemia is almost exclusively a disease of the aged. Malignant clones are predominantly CD5+ and autoantibody-producing. The amount of autoantibodies with higher affinity and more restricted binding, both organ-specific (e.g., thyroglobulin), and non-specific (e.g., DNA) also increase with aging. In one study, two-thirds of people over age 60 had either anti-nuclear antibodies, thyroglobulin antibody, or circulating rheumatoid factors. The amount of non-organ-specific autoantibody is highest in the elderly with chronic illness.
Hematogenous tumors
Eckart Haneke in Histopathology of the NailOnychopathology, 2017
Chronic lymphocytic leukemia typically occurs in elderly people and usually runs a protracted, relatively benign appearing course. Specific skin infiltrates on acral sites such as the hands, ears, or nose are common. They form large, soft, and red nodules that occasionally may ulcerate spontaneously or on trauma. When affecting the nail apparatus, it often looks like chronic paronychia.22–24 Subungual infiltrates cause an overcurvature25 and elevation of the nail plate.26 Clubbing and periosteal bone destruction of the distal phalanx were also seen.27 Nonspecific nail dystrophy occurs in up to one-quarter of the patients.28 The specific infiltrates respond well to irradiation.
Cancer
Spyridon E. Kintzios, Maria G. Barberaki, Evangelia A. Flampouri in Plants That Fight Cancer, 2019
Leukemia is distinguished in acute lymphocytic (common among children), acute myelogenous, and chronic lymphocytic leukemia. All cases are characterized by an abnormal proliferation of immature white blood cells produced in the lymphatic system (mainly in the bone marrow). The disease is associated with genetic abnormalities, viral infections, and exposure to environmental toxins or radiation. Although the survival rate for acute myelogenous leukemia (AML) has increased over time, it still varies among different subtypes of the disease as well as age (with older patients having a lower survival outlook).
What role for AHR activation in IL4I1-mediated immunosuppression ?
Published in OncoImmunology, 2021
Flavia Castellano, Armelle Prevost-Blondel, José L. Cohen, Valérie Molinier-Frenkel
The role of IL4I1 has been characterized in mouse models of transplanted and spontaneous melanoma, both in WT and IL4I1 deficient backgrounds, clearly showing that it facilitates tumor growth by inhibiting the antitumor cytotoxic T-cell response and remodeling the tumor immune microenvironment.9,10 These observations have been recently extended to a model of chronic lymphocytic leukemia.11 In line with this, clinical correlations have been reported between IL4I1 expression by stromal cells and invasion of the sentinel lymph nodes, a higher melanoma stage, and rapid relapse in human primary cutaneous melanomas, in which IL4I1 expression was analyzed by immunohistochemistry.12 Most interestingly, zones in which IL4I1 expression was concentrated were depleted of cytotoxic CD8+ T cells and enriched with regulatory FoxP3+ T cells. Moreover, IL4I1 was overexpressed in melanoma patients with progressive disease under treatment with the anti-PD-1 antibody nivolumab, suggesting a relation between IL4I1 expression and resistance to immune-checkpoint blockade.11
Potential of BCL2 as a target for chronic lymphocytic leukemia treatment
Published in Expert Review of Hematology, 2018
Riccardo Moia, Fary Diop, Chiara Favini, Ahad Ahmed Kodipad, Gianluca Gaidano
Chronic lymphocytic leukemia is a highly heterogeneous disease; some patients may never require treatment, whereas others relapse early after frontline therapeutic approaches.Molecular studies have allowed to better understand the pathogenesis of CLL. Apoptosis deregulation has emerged as one of the most commonly impaired pathways in the disease, and this biological feature has prompted the development of new drugs active in promoting the intrinsic pathway of apoptosis.Venetoclax, an orally bioavailable BCL2 inhibitor used both in monotherapy and in combination with other drugs, has allowed to obtain responses in the majority of patients, including those carrying TP53 disruption, with an acceptable toxicity profile.Future objectives will be i) the tailoring of treatment in relation to the unique risk profile of each patient; ii) the identification of long term side effects and of the molecular mechanism of venetoclax resistance; iii) in the perspective of global medicine, fostering the accessibility of venetoclax as a lifesaving drug to all those in clinical need.
Managing patients with hematological malignancies during COVID-19 pandemic
Published in Expert Review of Hematology, 2020
Certain specific characteristics are specified in the case of Chronic lymphocytic leukemia (CLL). First, it is usually a disease of old individuals with a median age at diagnosis ranging from 65–70 years [24]. Secondly, it is a B cell disorder and the associated hypogammaglobulinemia predisposes for increased risk of recurrent infections. CLL is the most common form of leukemia in the western world, and with the old age and other associated comorbidities, this population is likely to perform worse, however, this needs confirmation. Based on the International Workshop on Chronic Lymphocytic Leukemia (iwCLL), for those CLL patients in whom treatment is indicated, it is advisable to avoid intense regimens like fludarabine, cyclophosphamide, and rituximab (FCR) due to risk of severe myelosuppression [25]. Similarly, the monoclonal antibodies, such as rituximab and obinutuzumab, may lead to B-cell depletion, reduce the humoral immunity further, and hence are recommended to avoid. Several oral target agents are now available, such as ibrutinib (BTK inhibitor), acalabrutinib (a second-generation BTK inhibitor), and venetoclax for use in CLL which can be used either alone or in combination depending upon various patient or disease-related risk factors.