792P - The differences in immunogenicity of TP53 mutated endometrial-, high-grade serous ovarian- and triple negative breast carcinomas

Background

In order to investigate potential differences in immunogenicity between p53-mutated (p53mut) endometrial cancer (EC), p53mut high-grade serous ovarian cancer (HGSOC), and p53mut triple negative breast cancer (TNBC), we conducted a thorough examination of tumor mutational burden (TMB) and performed a comprehensive analysis of immune cells, cytokines, and expression of immune-modulating factors within these specific tumor entities. Our aim was to gain deeper insight into the potential differences in immunogenicity of these cancer types and their related response to immune checkpoint inhibitors (ICIs).

Methods

This study utilized data from the “The Cancer Genome Atlas” Network to conduct a retrospective analysis of three cohorts, including 608 females with p53mut EC, p53mut HGSOC, and p53mut TNBC. Patients were dichotomized along their respective median TMB. Univariate Kaplan–Meier analyses and multivariate Cox-regression survival analyses were used to explore the role of TMB in progression-free survival (PFS) and overall survival (OS). Differences in immune cell infiltration, cytokine- and other immune modulating expressions among the three tumor entities were examined using the Kruskal-Wallis test followed by a post hoc analysis and Pearson correlation.

Results

The high-TMB group in EC and HGSOC showed significantly longer PFS (EC HR 0.56, p=0.029; HGSOC HR 0.73, p=0.023) and OS (EC HR 0.48, p=0.022; HGSOC HR 0.62, p = 0.002). In TNBC OS was significantly longer in the high-TMB group. The results were confirmed in multivariate Cox-regression survival analyses. Higher levels of pro-tumoral, immunosuppressive cells, cytokines and immune-modulators were found in HGSOC and TNBC compared to EC, e.g. higher proportions of regulatory T cells and M2 tumor-associated macrophages, as well as increased expressions of C1qA, FOXP3, and XBP1.

Conclusions

Immune characteristics in immunosuppressive tumor immune microenvironment (TIME) differ substantially among the three investigated tumor entities in terms that p53mut EC exhibit fewer immunosuppressive traits, resulting in a higher likelihood of responding to immune checkpoint inhibitors despite its copy number high and low-TMB nature.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A.G. Zeimet: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, GSK, PharmaMar, Roche, Seagen, Eisai, Biontech, Pfizer; Financial Interests, Personal, Invited Speaker: MSD, Novartis. K. Leitner: Financial Interests, Personal, Other: Gilead, GSK, Eisai, Roche. B. Feroz: Financial Interests, Other, travel expenses: Roche, Pfizer, Lilly. C. Marth: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche Austria, Novartis, MSD, PharmaMar, GSK, Pfizer, ImmunoGen, Daiichi Sankyo, Biontech, Novocure, Eisai; Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, GSK, Novartis, MSD, PharmaMar, Roche, AstraZeneca, GSK; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche. K. Steger: Financial Interests, Other: Roche, Daiichi Sankyo, GSK, PharmaMar. All other authors have declared no conflicts of interest.