Chen Xiang/Han Leng/Liu Hong/Jing Ying collaborate to reveal gender-related differences in immune-related adverse reactions of cancer immunotherapy

In recent years, as more and more cancer patients adopt immunotherapy, immune related adverse events (irAE) have also attracted the attention of researchers.

There is evidence that there are gender differences in immune response, for example, autoimmune diseases are more common in women.

Small-scale data set studies published in the previous period have reached the opposite conclusion: some studies have pointed out that irAE occurs more frequently in women, and some studies have shown that irAE occurs more frequently in men.

Therefore, the scientific issue of whether there are gender differences in irAE urgently needs large-scale and multi-level data for in-depth discussion, which will help to clarify the status of gender-related factors in tumor immunotherapy.

In March 2021, Professor Chen Xiang and Professor Liu Hong from Xiangya Hospital of Central South University, Professor Han Leng from Texas A&M University, and Associate Researcher Jing Ying from the Clinical Research Center of Shanghai Jiaotong University School of Medicine jointly published a topic in the Journal of the National Cancer Institute This is the research paper of Association between sex and immune-related adverse events during immune checkpoint inhibitor therapy, which comprehensively analyzes the published clinical research data, FDA (US Food and Drug Administration Adverse Event Reporting System, FAERS) and WHO ( VigiBase)'s pharmacovigilance database and TCGA's tumor multi-omics data, and retrospectively analyzed two independent sample sets of tumor immunotherapy, in order to comprehensively identify the gender differences of irAE from different levels.

The author analyzed the above four different sources and different levels of data and found that irAE is not significantly different between men and women.

This comprehensive analysis provides new clinical research ideas and methods for urgent scientific research that urgently needs in-depth clinical understanding but lacks large-scale data.

This research result provides a theoretical basis for doctors to choose appropriate immunotherapy for patients, and has far-reaching clinical significance.

In this study, the author first used the random effects model to conduct a meta-analysis of 1,096 female immunotherapy patients and 1886 male immunotherapy patients in 13 published clinical studies, and found that irAE was not significantly different between men and women .

A subgroup analysis based on the types of immunotherapy drugs and the proportion of female patients also yielded consistent conclusions.

Next, the author used a logistic regression model to analyze the large-scale drug safety data of 12225 immunotherapy patients with 18 tumor types from FAERS and 10979 immunotherapy patients with 18 tumor types from VigiBase, and found that most of them Among tumor types, the reported rate of irAE was not significantly different between males and females.

The author also analyzed a single type of irAE and different grades of irAE, and found no difference between males and females.

Therefore, we further used the propensity scoring model to analyze the multi-omics data of 22 tumor types in the TCGA database, and further explored the difference between male and female irAE from the molecular level.

The multi-omics analysis also found that irAE-related factors and signaling pathways were not significantly different between men and women.

Finally, the author collected two independent retrospective study cohorts for propensity score analysis, and further independently verified the conclusion that irAE had no significant gender difference.

This series of results will prompt the scientific research community to re-evaluate the impact of gender factors on immune-related adverse reactions, and also provide a research example for the study of clinical problems that need to be resolved.

Figure 1.
Schematic diagram of using multi-level and multi-source data to study irAE gender differences.
Associate researcher Jing Ying, Associate Professor Zhang Yongchang, Professor Wang Jing, Professor Kunyan Li are the co-first authors of the article, Professor Han Leng, Professor Gordon Mills, Professor Chen Xiang and Professor Liu Hong is the co-corresponding author of the article.

The research team has published a series of original studies in the field of tumor immunotherapy in recent years.

For example, biomarkers of irAE in cancer immunotherapy (2020, Nature Communications, see BioArt report for details: Nat Comm | Han Leng/Zhuang Guanglei/Xue Xinxin's research group collaborated to identify biomarkers of immune-related adverse events in cancer immunotherapy), glands A new mechanism for the regulation of tumor PD-L1 by glycosides (2020, Cancer Cell, see BioArt report for details: Cancer Cell | Chen Xiang/Liu Hong cooperated to reveal a new mechanism for adenosine to regulate tumor PD-L1-PD-1 monoclonal antibody for melanoma patients Therapy provides new diagnosis and treatment strategies), gender-related molecular differences in cancer immunotherapy (2020, Nature Communications, see BioArt report for details: Nat Comm | Liu Hong/Ye Youqiong/Han Leng cooperates to reveal gender-related molecular differences in cancer immunotherapy), MMP regulation New tumor immune mechanism (2020, Genome Medicine, see BioArt report: Chen Xiang/Han Leng/Liu Hong/Ye Youqiong, etc.
reveal new mechanisms for MMP to regulate tumor immunity) and Sunitinib regulate tumor immunotherapy new mechanisms (2020, Advanced Science, see for details BioArt report: Adv Sci | Chen Xiang/Liu Jing/Liu Hong/Han Leng collaborated to reveal a new mechanism for tyrosine kinase receptor inhibitors to regulate tumor immunity).

Research Group of Professor Han Leng, Texas A&M University, USA (