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000182555 0247_ $$2doi$$a10.1016/j.ygyno.2022.10.022
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000182555 041__ $$aEnglish
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000182555 1001_ $$aMeagher, Nicola S$$b0
000182555 245__ $$aProfiling the immune landscape in mucinous ovarian carcinoma.
000182555 260__ $$aAmsterdam [u.a.]$$bElsevier$$c2022
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000182555 520__ $$aMucinous 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.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.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.In summary, MOCs are mostly immunogenically 'cold', suggesting they may have limited response to current immunotherapies.
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000182555 650_7 $$2Other$$aImmune infiltrate
000182555 650_7 $$2Other$$aMucinous ovarian carcinoma
000182555 650_7 $$2Other$$aRare histotype
000182555 7001_ $$aHamilton, Phineas$$b1
000182555 7001_ $$aMilne, Katy$$b2
000182555 7001_ $$aThornton, Shelby$$b3
000182555 7001_ $$aHarris, Bronwyn$$b4
000182555 7001_ $$aWeir, Ashley$$b5
000182555 7001_ $$aAlsop, Jennifer$$b6
000182555 7001_ $$aBisinoto, Christiani$$b7
000182555 7001_ $$aBrenton, James D$$b8
000182555 7001_ $$aBrooks-Wilson, Angela$$b9
000182555 7001_ $$aChiu, Derek S$$b10
000182555 7001_ $$aCushing-Haugen, Kara L$$b11
000182555 7001_ $$aFereday, Sian$$b12
000182555 7001_ $$aGarsed, Dale W$$b13
000182555 7001_ $$aGayther, Simon A$$b14
000182555 7001_ $$aGentry-Maharaj, Aleksandra$$b15
000182555 7001_ $$aGilks, Blake$$b16
000182555 7001_ $$aJimenez-Linan, Mercedes$$b17
000182555 7001_ $$aKennedy, Catherine J$$b18
000182555 7001_ $$aLe, Nhu D$$b19
000182555 7001_ $$aPiskorz, Anna M$$b20
000182555 7001_ $$aRiggan, Marjorie J$$b21
000182555 7001_ $$aShah, Mitul$$b22
000182555 7001_ $$aSingh, Naveena$$b23
000182555 7001_ $$aTalhouk, Aline$$b24
000182555 7001_ $$aWidschwendter, Martin$$b25
000182555 7001_ $$aBowtell, David D L$$b26
000182555 7001_ $$aCandido Dos Reis, Francisco J$$b27
000182555 7001_ $$aCook, Linda S$$b28
000182555 7001_ $$0P:(DE-He78)74a6af8347ec5cbd4b77e562e10ca1f2$$aFortner, Renée T$$b29$$udkfz
000182555 7001_ $$aGarcía, María J$$b30
000182555 7001_ $$aHarris, Holly R$$b31
000182555 7001_ $$aHuntsman, David G$$b32
000182555 7001_ $$aKarnezis, Anthony N$$b33
000182555 7001_ $$aKöbel, Martin$$b34
000182555 7001_ $$aMenon, Usha$$b35
000182555 7001_ $$aPharoah, Paul D P$$b36
000182555 7001_ $$aDoherty, Jennifer A$$b37
000182555 7001_ $$aAnglesio, Michael S$$b38
000182555 7001_ $$aPike, Malcolm C$$b39
000182555 7001_ $$aPearce, Celeste Leigh$$b40
000182555 7001_ $$aFriedlander, Michael L$$b41
000182555 7001_ $$aDeFazio, Anna$$b42
000182555 7001_ $$aNelson, Brad H$$b43
000182555 7001_ $$aRamus, Susan J$$b44
000182555 773__ $$0PERI:(DE-600)1467974-7$$a10.1016/j.ygyno.2022.10.022$$gVol. 168, p. 23 - 31$$p23 - 31$$tGynecologic oncology$$v168$$x0090-8258$$y2022
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