Molecular Aspects of Resistance to Immunotherapies—Advances in Understanding and Management of Diffuse Large B-Cell Lymphoma

Kusowska, Aleksandra; Kubacz, Matylda; Krawczyk, Marta; Ślusarczyk, Aleksander; Winiarska, Magdalena; Bobrowicz, Małgorzata

doi:10.3390/ijms23031501

Cited by 14 publications

(8 citation statements)

References 207 publications

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“…Vitamin D has been shown to modulate immune responses, including the activation and function of macrophages and NK cells involved in antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) [ 50 ]. Although studies highlight the potential benefits of vitamin D supplementation in patients with lymphomas, which may improve treatment efficacy and antitumor macrophage activity [ 51 ], further investigation is required to fully understand the mechanisms underlying the relationship between vitamin D levels and immune cell function in the context of lymphoid malignancies.…”

Section: Discussionmentioning

confidence: 99%

A Systematic Review Assessing the Impact of Vitamin D Levels on Adult Patients with Lymphoid Malignancies

et al. 2023

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Vitamin D deficiency has been correlated with various conditions, including the risk of developing lymphoid malignancies. This systematic review aimed to assess the association between vitamin D levels at diagnosis of lymphoid malignancies, patient outcomes, and survival. A systematic review was conducted, encompassing 15 studies published until January 2023, involving 4503 patients, examining the relationship between vitamin D and lymphoid cancers. The median age of the patients was 56.5 years, with a median follow-up duration of approximately 36 months across studies. The overall median vitamin D level at initial measurement was 20.4 ng/mL, while a <20 ng/mL threshold was used to define vitamin D insufficiency. The results demonstrated significant associations between vitamin D levels and patient outcomes in several lymphoid malignancies, with a pooled risk in disease progression of 1.93 and a pooled hazard ratio of 2.06 for overall survival in patients with 25-(OH)D levels below the normal threshold of 20 ng/mL. Among findings, it was demonstrated that supplemental vitamin D improves the chemosensitivity of tumors by reducing the rate of tumor growth compared with vitamin D or chemotherapy alone. Vitamin D had a protective effect for patients with DLBCL under R-CHOP treatment, while vitamin D insufficiency was associated with the impairment of rituximab treatment and showed worse clinical outcomes in chimeric antigen receptor T-cell (CAR-T) recipients. Although one study found no association between vitamin D deficiency and the cause of death, most associated vitamin D insufficiency with early clinical failure and lower survival probability. In conclusion, his systematic review highlights the importance of vitamin D levels in the prognosis and survival of patients with lymphoid malignancies. Further research is needed to better understand the underlying mechanisms and explore the potential benefits of vitamin D supplementation in managing these cancers.

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Section: Discussionmentioning

confidence: 99%

A Systematic Review Assessing the Impact of Vitamin D Levels on Adult Patients with Lymphoid Malignancies

et al. 2023

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“…Thus, in order to improve prognostic outcomes, new treatment option is under the preclinical trials. 56 , 77 , 79 …”

Section: Splicing Mutation and Targeted Drugs For The Treatment Of Dlbclmentioning

confidence: 99%

Role of RNA Splicing Mutations in Diffuse Large B Cell Lymphoma

Berta,

Girma,

Melku

et al. 2023

IJGM

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Ribonucleic acid splicing is a crucial process to create a mature mRNA molecule by removing introns and ligating exons. This is a highly regulated process, but any alteration in splicing factors, splicing sites, or auxiliary components affects the final products of the gene. In diffuse large B-cell lymphoma, splicing mutations such as mutant splice sites, aberrant alternative splicing, exon skipping, and intron retention are detected. The alteration affects tumor suppression, DNA repair, cell cycle, cell differentiation, cell proliferation, and apoptosis. As a result, malignant transformation, cancer progression, and metastasis occurred in B cells at the germinal center. B-cell lymphoma 7 protein family member A (BCL7A), cluster of differentiation 79B (CD79B), myeloid differentiation primary response gene 88 (MYD88), tumor protein P53 (TP53), signal transducer and activator of transcription (STAT), serum- and glucose-regulated kinase 1 (SGK1), Pou class 2 associating factor 1 (POU2AF1), and neurogenic locus notch homolog protein 1 (NOTCH) are the most common genes affected by splicing mutations in diffuse large B cell lymphoma.

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“…It is also important to note that CNVs of FcgRIIIa were not determined in these studies, which could significantly affect the homozygous counts of FcgRIIIa genotypes. In addition, the existence of other factors or mechanisms of resistance may influence the efficiency of ADCC in tumour eradication (87).…”

Section: Rituximabmentioning

confidence: 99%

Relevance of Fc Gamma Receptor Polymorphisms in Cancer Therapy With Monoclonal Antibodies

Mata-Molanes

Rebollo-Liceaga²,

Martínez-Navarro³

et al. 2022

Front. Oncol.

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Therapeutic monoclonal antibodies (mAbs), including immune checkpoint inhibitors (ICIs), are an important breakthrough for the treatment of cancer and have dramatically changed clinical outcomes in a wide variety of tumours. However, clinical response varies among patients receiving mAb-based treatment, so it is necessary to search for predictive biomarkers of response to identify the patients who will derive the greatest therapeutic benefit. The interaction of mAbs with Fc gamma receptors (FcγR) expressed by innate immune cells is essential for antibody-dependent cellular cytotoxicity (ADCC) and this binding is often critical for their in vivo efficacy. FcγRIIa (H131R) and FcγRIIIa (V158F) polymorphisms have been reported to correlate with response to therapeutic mAbs. These polymorphisms play a major role in the affinity of mAb receptors and, therefore, can exert a profound impact on antitumor response in these therapies. Furthermore, recent reports have revealed potential mechanisms of ICIs to modulate myeloid subset composition within the tumour microenvironment through FcγR-binding, optimizing their anti-tumour activity. The purpose of this review is to highlight the clinical contribution of FcγR polymorphisms to predict response to mAbs in cancer patients.

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Molecular Aspects of Resistance to Immunotherapies—Advances in Understanding and Management of Diffuse Large B-Cell Lymphoma

Cited by 14 publications

References 207 publications

A Systematic Review Assessing the Impact of Vitamin D Levels on Adult Patients with Lymphoid Malignancies

A Systematic Review Assessing the Impact of Vitamin D Levels on Adult Patients with Lymphoid Malignancies

Role of RNA Splicing Mutations in Diffuse Large B Cell Lymphoma

Relevance of Fc Gamma Receptor Polymorphisms in Cancer Therapy With Monoclonal Antibodies

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