Immune Dysfunctions and Immune-Based Therapeutic Interventions in Chronic Lymphocytic Leukemia

Griggio, Valentina; Perutelli, Francesca; Salvetti, Chiara; Boccellato, Elia; Boccadoro, Mario; Vitale, Candida; Coscia, Marta

doi:10.3389/fimmu.2020.594556

Cited by 50 publications

(51 citation statements)

References 289 publications

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“…Immunological dysfunction is known in patients with CLL and myeloma. This is either caused by innate immunodeficiency or induced by treatment leading to a lower rate of immunogenicity after vaccination 12,17–20 . A correlation between serological response and high NK‐cell count has already been described in pneumococcal polysaccharide vaccine (PPSV23) 21 .…”

Section: Discussionmentioning

confidence: 99%

“…This is either caused by innate immunodeficiency or induced by treatment leading to a lower rate of immunogenicity after vaccination. 12,[17][18][19][20] A correlation between serological response and high NK-cell count has already been described in pneumococcal polysaccharide vaccine (PPSV23). 21 The correlation between reduced antibody response in patients under treatment as well as low NK-cell and lymphocytes counts found in our present study could be interpreted as the immunosuppressive effect of systemic treatment used, especially in haematological diseases.…”

Section: Discussionmentioning

confidence: 99%

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Serological SARS‐CoV‐2 antibody response, potential predictive markers and safety of BNT162b2 mRNA COVID‐19 vaccine in haematological and oncological patients

et al. 2021

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Summary Haemato‐oncological patients are at risk in case of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection. Currently, vaccination is the best‐evaluated preventive strategy. In the present study, we aimed to assess serological response, predictive markers, and safety of BNT162b2 in haemato‐oncological patients. A total of 259 haemato‐oncological patients were vaccinated with two 30 µg doses of BNT162b2 administered 21 days apart. Serological response was assessed by ELECSYS® Anti‐SARS‐CoV‐2‐S immunoassay before vaccination, and at 3 and 7 weeks after the first dose (T1, T2). Safety assessment was performed. At T2 spike protein receptor binding domain (S/RBD) antibodies were detected in 71·4% of haematological and in 94·5% of oncological patients (P < 0·001). Haematological patients receiving systemic treatment had a 14·2‐fold increased risk of non‐responding (95% confidence interval 3·2–63·3, P = 0·001). Subgroups of patients with lymphoma or chronic lymphocytic leukaemia were at highest risk of serological non‐response. Low immunoglobulin G (IgG) level, lymphocyte‐ and natural killer (NK)‐cell counts were significantly associated with poor serological response (P < 0·05). Vaccination was well tolerated with only 2·7% of patients reporting severe side‐effects. Patients with side‐effects developed a higher S/RBD‐antibody titre compared to patients without side‐effects (P = 0·038). Haematological patients under treatment were at highest risk of serological non‐response. Low lymphocytes, NK cells and IgG levels were found to be associated with serological non‐response. Serological response in oncological patients was encouraging. The use of BNT162b2 is safe in haemato‐oncological patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Serological SARS‐CoV‐2 antibody response, potential predictive markers and safety of BNT162b2 mRNA COVID‐19 vaccine in haematological and oncological patients

et al. 2021

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“…Therapies with an improved efficacy prolong patients' survival and confer a longer follow-up duration, thus increasing the possibility to detect disease-related complications over a longer period of time. Targeted drugs-which along with their anti-tumor activity exert multiple off-target effects on different components of the immune system and tumor microenvironment (reviewed in [1,2,185,186])-may also directly impact on the risk of immune dysfunctions and immune-dependent clinical manifestations. Therefore, we expect that the current wide use of these compounds in the clinical practice and the progressively growing follow-up duration will provide more data and pieces of information to be added to this complex scenario.…”

Section: Discussionmentioning

confidence: 99%

“…Natural Killer (NK) cells are fundamental components of the innate immune system and play an important role in antitumor immunity, being able to kill neoplastic cells without priming or prior activation [1,62]. However, the activity of NK cells, which is regulated by activating and inhibitory signals, is disrupted in malignant environments [63].…”

Section: Natural Killer and Natural Killer T Cells 221 Natural Killer Cellsmentioning

confidence: 99%

“…Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disease typically characterized by a wide spectrum of immune alterations, affecting both innate and adaptive immunity (reviewed in [1]). In addition to being a hallmark of the disease, CLL-associated immune dysfunctions strongly impact the immune surveillance, facilitate tumor progression and eventually affect the disease course.…”

Section: Introductionmentioning

confidence: 99%

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Impact of Immune Parameters and Immune Dysfunctions on the Prognosis of Patients with Chronic Lymphocytic Leukemia

Vitale

Boccellato

Comba

et al. 2021

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Chronic lymphocytic leukemia (CLL) is characterized by a wide spectrum of immune alterations, affecting both the innate and adaptive immunity. These immune dysfunctions strongly impact the immune surveillance, facilitate tumor progression and eventually affect the disease course. Quantitative and functional alterations involving conventional T cells, γδ T cells, regulatory T cells, NK and NKT cells, and myeloid cells, together with hypogammaglobulinemia, aberrations in the complement pathways and altered cytokine signature have been reported in patients with CLL. Some of these immune parameters have been shown to associate with other CLL-related characteristics with a known prognostic relevance or to correlate with disease prognosis. Also, in CLL, the complex immune response dysfunctions eventually translate in clinical manifestations, including autoimmune phenomena, increased risk of infections and second malignancies. These clinical issues are overall the most common complications that affect the course and management of CLL, and they also may impact overall disease prognosis.

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Induction of neutralizing antibodies in CLL patients after SARS-CoV-2 mRNA vaccination: a monocentric experience

et al. 2022

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Vaccination represents the best strategy to fight COVID-19 pandemics, especially in immune compromised subjects. In chronic lymphatic leukemia patients, a marked impairment of the immune response to mRNA SARS-CoV-2 vaccine was observed. In this report, we analyzed anti-RBD and neutralizing antibodies in CLL patients after two doses of mRNA SARS CoV 2 vaccine and evaluated the impact of Bruton kinase inhibitory agents. Twenty-seven CLL patients vaccinated with mRNA vaccines against SARS CoV-2 were recruited. Serum IgG, IgM and IgA anti-RBD antibodies and neutralizing antibodies were detected, and antibody avidity was measured. Peripheral blood leukocytes subsets were evaluated by flow cytometry. After two vaccine doses anti-RBD IgG were produced in 11/27 (40.5%) of patients and levels of IgG and IgA anti RBD in CLL patients were sensibly lower than in controls. Neutralizing antibodies were detectable in 12/27 (44.5%) of the patients and their level was lower than that observed in controls. Disease burden and treatment with Bruton kinases inhibitors markedly impaired vaccine induced antibody response. However, in responder patients, antibody avidity was comparable to normal subjects, indicating that the process of clonal selection and affinity maturation takes place as expected. Taken together, these data confirm the impact of disease burden and therapy on production of anti-RBD and neutralizing antibodies and support the current policy of vaccinating CLL patients.

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Immune Dysfunctions and Immune-Based Therapeutic Interventions in Chronic Lymphocytic Leukemia

Cited by 50 publications

References 289 publications

Serological SARS‐CoV‐2 antibody response, potential predictive markers and safety of BNT162b2 mRNA COVID‐19 vaccine in haematological and oncological patients

Serological SARS‐CoV‐2 antibody response, potential predictive markers and safety of BNT162b2 mRNA COVID‐19 vaccine in haematological and oncological patients

Impact of Immune Parameters and Immune Dysfunctions on the Prognosis of Patients with Chronic Lymphocytic Leukemia

Induction of neutralizing antibodies in CLL patients after SARS-CoV-2 mRNA vaccination: a monocentric experience

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