Dataset Information

Profiling the immune landscape in mucinous ovarian carcinoma.

ABSTRACT:

Objective

Mucinous ovarian carcinoma (MOC) is a rare histotype of ovarian cancer, with low response rates to standard chemotherapy, and very poor survival for patients diagnosed at advanced stage. There is a limited understanding of the MOC immune landscape, and consequently whether immune checkpoint inhibitors could be considered for a subset of patients.

Methods

We performed multicolor immunohistochemistry (IHC) and immunofluorescence (IF) on tissue microarrays in a cohort of 126 MOC patients. Cell densities were calculated in the epithelial and stromal components for tumor-associated macrophages (CD68+/PD-L1+, CD68+/PD-L1-), T cells (CD3+/CD8-, CD3+/CD8+), putative T-regulatory cells (Tregs, FOXP3+), B cells (CD20+/CD79A+), plasma cells (CD20-/CD79a+), and PD-L1+ and PD-1+ cells, and compared these values with clinical factors. Univariate and multivariable Cox Proportional Hazards assessed overall survival. Unsupervised k-means clustering identified patient subsets with common patterns of immune cell infiltration.

Results

Mean densities of PD1+ cells, PD-L1- macrophages, CD4+ and CD8+ T cells, and FOXP3+ Tregs were higher in the stroma compared to the epithelium. Tumors from advanced (Stage III/IV) MOC had greater epithelial infiltration of PD-L1- macrophages, and fewer PD-L1+ macrophages compared with Stage I/II cancers (p = 0.004 and p = 0.014 respectively). Patients with high epithelial density of FOXP3+ cells, CD8+/FOXP3+ cells, or PD-L1- macrophages, had poorer survival, and high epithelial CD79a + plasma cells conferred better survival, all upon univariate analysis only. Clustering showed that most MOC (86%) had an immune depleted (cold) phenotype, with only a small proportion (11/76,14%) considered immune inflamed (hot) based on T cell and PD-L1 infiltrates.

Conclusion

In summary, MOCs are mostly immunogenically 'cold', suggesting they may have limited response to current immunotherapies.

SUBMITTER: Meagher NS

PROVIDER: S-EPMC10374276 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

Profiling the immune landscape in mucinous ovarian carcinoma.

Meagher Nicola S NS Hamilton Phineas P Milne Katy K Thornton Shelby S Harris Bronwyn B Weir Ashley A Alsop Jennifer J Bisinoto Christiani C Brenton James D JD Brooks-Wilson Angela A Chiu Derek S DS Cushing-Haugen Kara L KL Fereday Sian S Garsed Dale W DW Gayther Simon A SA Gentry-Maharaj Aleksandra A Gilks Blake B Jimenez-Linan Mercedes M Kennedy Catherine J CJ Le Nhu D ND Piskorz Anna M AM Riggan Marjorie J MJ Shah Mitul M Singh Naveena N Talhouk Aline A Widschwendter Martin M Bowtell David D L DDL Candido Dos Reis Francisco J FJ Cook Linda S LS Fortner Renée T RT García María J MJ Harris Holly R HR Huntsman David G DG Karnezis Anthony N AN Köbel Martin M Menon Usha U Pharoah Paul D P PDP Doherty Jennifer A JA Anglesio Michael S MS Pike Malcolm C MC Pearce Celeste Leigh CL Friedlander Michael L ML DeFazio Anna A Nelson Brad H BH Ramus Susan J SJ

Gynecologic oncology 20221108

<h4>Objective</h4>Mucinous ovarian carcinoma (MOC) is a rare histotype of ovarian cancer, with low response rates to standard chemotherapy, and very poor survival for patients diagnosed at advanced stage. There is a limited understanding of the MOC immune landscape, and consequently whether immune checkpoint inhibitors could be considered for a subset of patients.<h4>Methods</h4>We performed multicolor immunohistochemistry (IHC) and immunofluorescence (IF) on tissue microarrays in a cohort of 12 ...[more]

PMID: 36368129

Similar Datasets

Project description:BackgroundPrevious clinical trials regarding the therapy in epithelial ovarian tumors have involved patients with all types of ovarian tumors. Mucinous borderline tumors may progress to invasive carcinoma even after therapy and Patients with mucinous ovarian cancer (MOC) often have a worse prognosis. Our objectives were to investigate the use of hyperthermic intraperitoneal perfusion therapy (HIPE) and the clinicopathological features of mucinous borderline ovarian tumor (MBOT) and MOC.MethodsA retrospective study was conducted on 240 patients with MBOT or MOC. The clinicopathologic feature included age, preoperative serum tumor markers, surgical procedures, surgical and pathological staging, frozen pathology, treatment, and recurrence. The effect of HIPE in MBOT and MOC were examined and the occurrence of adverse events was analyzed.ResultsThe median age was 34 years in 176 MBOT patients. Some 40.1% of patients had elevated CA125, 40.2% had elevated CA199, and 5.6% had elevated HE4. The accuracy rate for frozen pathology of resected specimen was 43.8%. The was no statistical difference in the recurrence rate between fertility-sparing and non-fertility-sparing surgery. Due to a short follow-up time in the HIPE group, no significant recurrence rate was found. The median age was 59 years in 64 MOC patients. Some 90.5% patients had elevated CA125, 95.3% had elevated CA199, and 75% had elevated HE4. There were 28 patients diagnosed with Federation International of Gynecology and Obstetrics (FIGO) stage I or II. For FIGO stage III and IV patients, the median progression-free survival (PFS) was 27 months in the HIPE group and the median overall survival (OS) in patients treated with HIPE was 53 months, which was significantly longer than that the other group (19 and 42 months). There was no severe fatal complication in all HIPE group.ConclusionsMBOT was usually diagnosed at an early stage and has a good prognosis. Hyperthermic intraperitoneal perfusion chemotherapy (HIPEC) can improve the survival of patients with advanced MOC and is safety. Combined use of CA125, CA199, HE4 can assist in the differential diagnosis of mucinous borderline neoplasms and mucinous carcinoma. Randomized studies evaluating dense HIPEC in the management of advanced ovarian cancer should be warranted.

Dataset Information

Profiling the immune landscape in mucinous ovarian carcinoma.

Objective

Methods

Results

Conclusion

Publications

Profiling the immune landscape in mucinous ovarian carcinoma.

Similar Datasets

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