Effect of Gender on the Outcome of Patients Receiving Immune Checkpoint Inhibitors for Advanced Cancer: A Systematic Review and Meta-Analysis of Phase III Randomized Clinical Trials

Grassadonia, Antonino; Sperduti, Isabella; Vici, Patrizia; Iezzi, Laura; Brocco, Davide; Gamucci, Teresa; Pizzuti, Laura; Maugeri‐Saccà, Marcello; Marchetti, Paolo; Cognetti, Gaetana; Tursi, Michele De; Natoli, Clara; Barba, Maddalena; Tinari, Nicola

doi:10.20944/preprints201808.0307.v2

Cited by 7 publications

(3 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This result is consistent with that of a previous study by Ye et al (2020). We attribute this to the fact that women tend to have stronger triggered and sustained immune responses against infections and have an increased propensity to develop autoimmune diseases compared to men (Grassadonia et al, 2018). Moreover, in the general population, there are differences in physiological factors, hormone levels, and hemoglobin levels between men and women, and women may be more susceptible to hematologic disorders (Rushton and Barth, 2010).…”

Section: Figuresupporting

confidence: 92%

Hematologic and lymphatic system toxicities associated with immune checkpoint inhibitors: a real-world study

Li,

Feng,

Chen

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

Introduction: Immune checkpoint inhibitors (ICIs) exert antitumor responses in many types of cancer but may also induce serious or fatal toxicities that affect all organ systems, including the hematologic and lymphatic systems. However, the risk of hematologic and lymphatic system toxicities following different ICI treatments remains unknown. This study aimed to describe the hematologic and lymphatic system toxicities associated with different ICI regimens and the impact of combining ICIs with anti-vascular endothelial growth factor drugs using the United States Food and Drug Administration Adverse Event Reporting System pharmacovigilance database.Methods: The reporting odds ratio (ROR) and information component (IC) indices were used to identify disproportionate reporting of ICI-associated hematologic and lymphatic adverse events (AEs).Results: We extracted 10,971 ICI-associated hematologic and lymphatic AEs from 35,417,155 reports. These AEs were more frequently reported in female patients (ROR: 1.04 95% confidence interval [CI]: 1.01–1.07) and younger patients (ROR: 1.05 95% CI: 1.01–1.09). The disseminated intravascular coagulation fatality rate (63.97%) was the highest among the reported preferred terms, despite its low incidence (3.32%). The time to onset of ICI-related hematologic and lymphatic AEs was relatively short, with 77.44% reported within 3 months. Disproportionate analysis showed that most ICIs were associated with significant overreporting of hematologic and lymphatic AEs (IC025: 0.34 and ROR025: 2.10). Hematologic and lymphatic system AEs were more frequently reported in patients treated with anti-programmed cell death protein 1/programmed cell death ligand 1 monotherapy than in those treated with anti-cytotoxic T-lymphocyte-associated protein 4 monotherapy (ROR: 1.54, 95% CI: 1.38–1.71), with atezolizumab showing the strongest signal (ROR025: 4.19, IC025: 1.00). In patients receiving combined treatment, ICIs plus bevacizumab exerted a higher disproportion signal than monotherapy (ROR: 161, 95% CI: 1.75–1.88).Discussion: The spectrum of hematologic and lymphatic AEs differed according to the ICI regimen. Early recognition and management of ICI-related hematologic and lymphatic AEs are vital in clinical practice.

show abstract

Section: Figuresupporting

confidence: 92%

Hematologic and lymphatic system toxicities associated with immune checkpoint inhibitors: a real-world study

Li,

Feng,

Chen

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…These suggested that therapies targeted at boosting immune responses will be less effective in female patients. On the other hand, phase III randomized clinical trials reported that sex-related factors may not affect the efficacy of ICB in melanoma patients ( 133 ). These contrasting results may be based on sample size or an inherent disparity in cancer etiology.…”

Section: Future Perspectives and Current Challenges With Hdac Inhibitors In Cancer Immunotherapymentioning

confidence: 99%

Regulating Histone Deacetylase Signaling Pathways of Myeloid-Derived Suppressor Cells Enhanced T Cell-Based Immunotherapy

2022

View full text Add to dashboard Cite

Immunotherapy has emerged as a promising approach to combat immunosuppressive tumor microenvironment (TME) for improved cancer treatment. FDA approval for the clinical use of programmed death receptor 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors revolutionized T cell-based immunotherapy. Although only a few cancer patients respond to this treatment due to several factors including the accumulation of immunosuppressive cells in the TME. Several immunosuppressive cells within the TME such as regulatory T cells, myeloid cells, and cancer-associated fibroblast inhibit the activation and function of T cells to promote tumor progression. The roles of epigenetic modifiers such as histone deacetylase (HDAC) in cancer have long been investigated but little is known about their impact on immune cells. Recent studies showed inhibiting HDAC expression on myeloid-derived suppressor cells (MDSCs) promoted their differentiation to less suppressive cells and reduced their immunosuppressive effect in the TME. HDAC inhibitors upregulated PD-1 or PD-L1 expression level on tumor or immune cells sensitizing tumor-bearing mice to anti-PD-1/PD-L1 antibodies. Herein we discuss how inhibiting HDAC expression on MDSCs could circumvent drawbacks to immune checkpoint inhibitors and improve cancer immunotherapy. Furthermore, we highlighted current challenges and future perspectives of HDAC inhibitors in regulating MDSCs function for effective cancer immunotherapy.

show abstract

“…Some of these are basic patient characteristics, including age, gender, and clinical history. [115][116][117] Distinct molecular markers, such as the intra-tumor expression of PD-L1 are predictive for therapy outcome when using pembrolizumab for treating NSCLC or cervical cancer. 36,[118][119][120] Recently, the impact of gut microbiome composition on ICI outcome has also gained significant attention.…”

Section: Identifying Predictive Factors For Ici Therapy Outcomesmentioning

confidence: 99%

Negative trade-off between neoantigen repertoire breadth and the specificity of HLA-I molecules shapes antitumor immunity

Balogh

View full text Add to dashboard Cite

show abstract

Effect of Gender on the Outcome of Patients Receiving Immune Checkpoint Inhibitors for Advanced Cancer: A Systematic Review and Meta-Analysis of Phase III Randomized Clinical Trials

Cited by 7 publications

References 37 publications

Hematologic and lymphatic system toxicities associated with immune checkpoint inhibitors: a real-world study

Hematologic and lymphatic system toxicities associated with immune checkpoint inhibitors: a real-world study

Regulating Histone Deacetylase Signaling Pathways of Myeloid-Derived Suppressor Cells Enhanced T Cell-Based Immunotherapy

Negative trade-off between neoantigen repertoire breadth and the specificity of HLA-I molecules shapes antitumor immunity

Contact Info

Product

Resources

About