Advances in sex disparities for cancer immunotherapy: unveiling the dilemma of Yin and Yang

Ma, Junfu; Yao, Yanxin; Chen, Kexin; Liu, Ben

doi:10.1186/s13293-022-00469-5

Cited by 12 publications

(8 citation statements)

References 115 publications

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“…Additionally, our study noted the inadequate consideration of sex in treatment decisions. However, the lack of detailed treatment information in the SEER database, such as immunotherapy choices, restricts a thorough analysis of the impact of treatment choices on different sexes (15,38,42). In addition, the SEER database does not provide molecular-level data on sex differences in genetic mutations, transcriptomics, metabolomics, or epigenetics, which are essential for a deeper understanding of the underlying sex-based disparities (22,43).…”

Section: Discussionmentioning

confidence: 99%

Sex differences in the incidence, mortality, and survival outcomes of lymphoma subtypes

Xing,

Cao,

et al. 2024

Preprint

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Background The phenomenon of males exhibiting higher lymphoma incidence and mortality rates than females has been widely recognized, and many survival analyses of certain lymphoma subtypes have incorporated sex as a critical prognostic determinant. However, comprehensive research on these sex-based differences in lymphomas remains limited. Methods This study aimed to conduct an integrated population-based analysis of sex-based disparities across various lymphoma subtypes using the Surveillance, Epidemiology, and End Results (SEER) database. We assessed the age-adjusted incidence rates of cases in the SEER22 and incidence-based mortality rates in the SEER12. The rates were stratified according to subtype, sex, race/ethnicity (incidence and mortality), age at diagnosis, and year of diagnosis (incidence only). Furthermore, we compared the risks of all-cause mortality, cancer-specific mortality, and cardiovascular disease-related mortality based on sex in SEER17. Results Our findings revealed that males had a higher likelihood of developing lymphoma and exhibited higher mortality rates than females for most lymphoma subtypes. These sex-based disparities in incidence and mortality were relatively consistent across five racial/ethnic groups. However, sex-based disparities in cancer incidence varied among age groups, and a trend toward narrowing differences with increasing age was observed in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), mantle cell lymphoma, and Burkitt lymphoma. Over the past two decades, trends in sex-based disparities of lymphoma incidence have remained stable. Regarding survival outcomes, males faced an increased risk of death compared to females for most lymphoma subtypes, except for NLPHL. Conclusions The results of our study underscore the complex and multifaceted nature of sex-based disparities in lymphoma and may offer valuable guidance for future research to unravel the potential causes of these differences.

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Section: Discussionmentioning

confidence: 99%

Sex differences in the incidence, mortality, and survival outcomes of lymphoma subtypes

Xing,

Cao,

et al. 2024

Preprint

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“…Sex hormones can also shape the interaction between the immune system and genes, extending their influence at the epigenetic level [ 37 ]. In RCC, sex-specific mutation spectra emerged and involved mutations of X chromosome encoded genes, such as KDM5C , and chromatin remodeling genes with epigenetic effects, such as BAP1 .…”

Section: Discussionmentioning

confidence: 99%

Sex and survival outcomes in patients with renal cell carcinoma receiving first-line immune-based combinations

Incorvaia,

Monteiro,

Massari

et al. 2024

Cancer Immunol Immunother

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Background There is an ongoing debate as to whether sex could be associated with immune checkpoint inhibitor (ICI) benefit. Existing literature data reveal contradictory results, and data on first-line immune combinations are lacking. Method This was a real-world, multicenter, international, observational study to determine the sex effects on the clinical outcomes in metastatic renal cell carcinoma (mRCC) patients treated with immuno-oncology combinations as first-line therapy. Results A total of 1827 mRCC patients from 71 cancer centers in 21 countries were included. The median OS was 38.7 months (95% CI 32.7–44.2) in the overall study population: 40.0 months (95% CI 32.7–51.6) in males and 38.7 months (95% CI 26.4–41.0) in females (p = 0.202). The median OS was higher in males vs. females in patients aged 18-49y (36.9 months, 95% CI 29.0–51.6, vs. 24.8 months, 95% CI 16.8–40.4, p = 0.426, with + 19% of 2y-OS rate, 72% vs. 53%, p = 0.006), in the clear cell histology subgroup (44.2 months, 95% CI 35.8–55.7, vs. 38.7 months, 95% CI 26.0–41.0, p = 0.047), and in patients with sarcomatoid differentiation (34.4 months, 95% CI 26.4–59.0, vs. 15.3 months, 95% CI 8.9–41.0, p < 0.001). Sex female was an independent negative prognostic factor in the sarcomatoid population (HR 1.72, 95% CI 1.15 − 2.57, p = 0.008). Conclusions Although the female’s innate and adaptive immunity has been observed to be more active than the male’s, women in the subgroup of clear cell histology, sarcomatoid differentiation, and those under 50 years of age showed shorter OS than males.

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“…The activated CD4 T cell is negatively correlated with the risk score and may facilitate cancer immunotherapy by improving cytotoxic T cell response (55). Immune checkpoints molecules, including anticytotoxic T lymphocyte antigen-4 (CTLA-4), anti-programmed cell death-1 (PD-1), and anti-programmed cell death ligand-1 (PD-L1), are the thoroughly investigated class of immunotherapy (56,57). TMB and MSI, independent of expression of PD-L1, are widely applied biomarkers in immunotherapy of cancer (58).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of autophagy-related clusters and individual risk model for immunotherapy response prediction in gastric cancer

Yao

Hu²,

Ma³

et al. 2023

Front. Oncol.

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IntroductionAutophagy can be triggered by oxidative stress and is a double-edged sword involved in the progression of multiple malignancies. However, the precise roles of autophagy on immune response in gastric cancer (GC) remain clarified.MethodsWe endeavor to explore the novel autophagy-related clusters and develop a multi-gene signature for predicting the prognosis and the response to immunotherapy in GC. A total of 1505 patients from eight GC cohorts were categorized into two subtypes using consensus clustering. We compare the differences between clusters by the multi-omics approach. Cox and LASSO regression models were used to construct the prognostic signature.ResultsTwo distinct clusters were identified. Compared with cluster 2, the patients in cluster 1 have favorable survival outcomes and lower scores for epithelial-mesenchymal transition (EMT). The two subtypes are further characterized by high heterogeneity concerning immune cell infiltration, somatic mutation pattern, and pathway activity by gene set enrichment analysis (GSEA). We obtained 21 autophagy-related differential expression genes (DEGs), in which PTK6 amplification and BCL2/CDKN2A deletion were highly prevalent. The four-gene (PEA15, HSPB8, BNIP3, and GABARAPL1) risk signature was further constructed with good predictive performance and validated in 3 independent datasets including our local Tianjin cohort. The risk score was proved to be independent prognostic factor. A prognostic nomogram showed robust validity of GC survival. The risk score was significantly associated with immune cell infiltration status, tumor mutation burden (TMB), microsatellite instability (MSI), and immune checkpoint molecules. Furthermore, the model was efficient for predicting the response to tumor-targeted agent and immunotherapy and verified by the IMvigor210 cohort. This model is also capable of discriminating between low and high-risk patients receiving chemotherapy.ConclusionAltogether, our exploratory research on the landscape of autophagy-related patterns may shed light on individualized therapies and prognosis in GC.

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Advances in sex disparities for cancer immunotherapy: unveiling the dilemma of Yin and Yang

Cited by 12 publications

References 115 publications

Sex differences in the incidence, mortality, and survival outcomes of lymphoma subtypes

Sex differences in the incidence, mortality, and survival outcomes of lymphoma subtypes

Sex and survival outcomes in patients with renal cell carcinoma receiving first-line immune-based combinations

Comprehensive analysis of autophagy-related clusters and individual risk model for immunotherapy response prediction in gastric cancer

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