Gender Differences and Their Effects on Survival Outcomes in Lung Cancer Patients Treated With PD-1/PD-L1 Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

Madala, Samragnyi; Rasul, R; Singla, K; Sison, C P; Seetharamu, Nagashree; Castellanos, Mario R.

doi:10.1016/j.clon.2022.03.010

Cited by 13 publications

(7 citation statements)

References 36 publications

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“…In contrast, a meta-analysis carried out by Conforti et al showed longer OS in women than in men treated with ICBs; however, this study excluded a large number of female patients from their final analysis, making interpretation of the results difficult [ 119 ]. Multiple other meta-analyses show no benefit of ICBs as monotherapies or as combinational therapies in males vs. females with lung cancer [ 120 , 121 ]. The lack of agreement on the effects of immunotherapies on males vs. females suggests a need for continued research into this issue and better powered studies to elucidate potential sex differences.…”

Section: Differences In Response To Therapymentioning

confidence: 99%

Sex Differences in Lung Cancer

May,

Shows,

Nana-Sinkam

et al. 2023

Cancers

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Sex disparities in the incidence and mortality of lung cancer have been observed since cancer statistics have been recorded. Social and economic differences contribute to sex disparities in lung cancer incidence and mortality, but evidence suggests that there are also underlying biological differences that contribute to the disparity. This review summarizes biological differences which could contribute to the sex disparity. Sex hormones and other biologically active molecules, tumor cell genetic differences, and differences in the immune system and its response to lung cancer are highlighted. How some of these differences contribute to disparities in the response to therapies, including cytotoxic, targeted, and immuno-therapies, is also discussed. We end the study with a discussion of our perceived future directions to identify the key biological differences which could contribute to sex disparities in lung cancer and how these differences could be therapeutically leveraged to personalize lung cancer treatment to the individual sexes.

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Section: Differences In Response To Therapymentioning

confidence: 99%

Sex Differences in Lung Cancer

May,

Shows,

Nana-Sinkam

et al. 2023

Cancers

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“…This survival advantage in malignant disease was shown before in diverse entities. [34][35][36][37] To date, a multifactorial cause such as gender-specific, biological and socio-cultural features is assumed. 34 In addition, location of the primary tumour might have an influence on prognosis.…”

Section: Discussionmentioning

confidence: 99%

Sarcoma Patients Admitted to the Intensive Care Unit (ICU): Predictive Relevance of Common Sepsis and Performance Parameters

Binder¹,

Brandes²,

Rau³

et al. 2023

CMAR

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Prognosis of sarcoma patients is improving, with a better understanding of sarcomagenesis revealing novel therapeutic targets. However, aggressive chemotherapy remains an essential part of treatment, bearing the risk of severe side effects that require intensive medical treatment. Available data on the characteristics and clinical outcome of sarcoma patients admitted to intensive care units (ICU) are sparse. Patients and Methods: We performed a retrospective analysis of sarcoma patients admitted to the ICU from 2005 to 2022. Patients ≥18 years with histologically proven sarcoma were included in our study. Results: Sixty-six patients were eligible for analysis. The following characteristics had significant impact on overall survival: sex (p=0.046), tumour localization (p=0.02), therapeutic intention (p=0.02), line of chemotherapy (p<0.001), SAPS II score (p=0.03) and SOFA score (p=0.02). Conclusion:Our study confirms the predictive relevance of established sepsis and performance scores in sarcoma patients. For overall survival, common clinical characteristics are also of significant value. Further investigation is needed to optimize ICU treatment of sarcoma patients.

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“…Sex differences in drug-response have been reported regarding the benefit of female patients when treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) (42). With regard to ICI, contradictory results have been reported (43, 44). Additional factors that influence a therapeutic response also include patient characteristics like ethnicity, body mass index (BMI) or the disease-context (45).…”

Section: Discussionmentioning

confidence: 99%

The pregnancy-associated protein glycodelin as a potential sex-specific target for resistance to immunotherapy in non-small cell lung cancer

Richtmann

Marwitz

Muley

et al. 2023

Preprint

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Lung cancer has been shown to be targetable by novel immunotherapies which reactivate the immune system and enable tumor cell killing. However, only few patients respond to this promising approach that has the potential to cure even metastatic disease. We hypothesize that the success of the treatment is impaired by the presence of immunosuppressors in the tumor microenvironment and therefore investigated the role of the immunosuppressive glycoprotein glycodelin that is expressed in patients with non-small-cell lung cancer (NSCLC). We demonstrate that the glycan pattern of NSCLC-derived glycodelin detected by a lectin-based enrichment assay highly resembles amniotic fluid-derived glycodelin A, which is known to have immunosuppressive properties. Binding assays with different leucocyte cell lines and subsequent transcriptome analyses reveal that glycodelin indeed interacts with immune cellsin vitroand regulates the expression of genes associated with inflammatory and tumor microenvironment pathways. Furthermore, multiplex immunofluorescence staining of glycodelin and different leucocytes in tumor microarray samples of patients with NSCLC show that glycodelin binds to tumor infiltrating CD8+ T cells and pro-tumorigenic M2 macrophages. Interestingly, we observe that high serum concentrations of glycodelin prior to immunotherapy are associated with a poor progression-free survival (p < 0.001) of female patients receiving PD-(L)1 inhibitors. Our findings demonstrate that glycodelin not only is a promising immunological biomarker for early identification of female patients that do not benefit from the costly immunotherapy, but also represents a promising immunotherapeutic target in NSCLC to improve therapeutic options in lung cancer.

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Gender Differences and Their Effects on Survival Outcomes in Lung Cancer Patients Treated With PD-1/PD-L1 Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

Cited by 13 publications

References 36 publications

Sex Differences in Lung Cancer

Sex Differences in Lung Cancer

Sarcoma Patients Admitted to the Intensive Care Unit (ICU): Predictive Relevance of Common Sepsis and Performance Parameters

The pregnancy-associated protein glycodelin as a potential sex-specific target for resistance to immunotherapy in non-small cell lung cancer

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