Serum CD95L Level Correlates with Tumor Immune Infiltration and Is a Positive Prognostic Marker for Advanced High-Grade Serous Ovarian Cancer. De La Motte Rouge, T., Corné, J., Cauchois, A., Le Boulch, M., Poupon, C., Henno, S., Rioux-Leclercq, N., Le Pabic, E., Laviolle, B., Catros, V., Levêque, J., Fautrel, A., Le Gallo, M., Legembre, P., & Lavoué, V. Molecular Cancer Research, 17(12):2537–2548, December, 2019.
Serum CD95L Level Correlates with Tumor Immune Infiltration and Is a Positive Prognostic Marker for Advanced High-Grade Serous Ovarian Cancer [link]Paper  doi  abstract   bibtex   
Abstract Soluble CD95L (s-CD95L) is a chemoattractant for certain lymphocyte subpopulations. We examined whether this ligand is a prognostic marker for high-grade serous ovarian cancer (HGSOC) and whether it is associated with accumulation of immune cells in the tumor. Serum s-CD95L levels in 51 patients with advanced ovarian cancer were tested by ELISA. IHC staining of CD3, CD4, CD8, CD20, CD163, CD31, FoxP3, CCR6, IL-17, Granzyme B, PD-L1, and membrane CD95L was used to assess tumor-infiltrating immune cells. Although the intensity of CD3, CD8, CD4, CD20, and CD163 in tumor tissues remained constant regardless of membrane CD95L expression, tumors in patients with HGSOC with s-CD95L levels ≥516 pg/mL showed increased infiltration by CD3+ T cells (P = 0.001), comprising both cytotoxic CD8+ (P = 0.01) and CD4+ (P = 0.0062) cells including FoxP3+ regulatory T cells (P = 0.0044). Also, the number of tumor-infiltrating CD20+ B cells (P = 0.0094) increased in these patients. Multivariate analyses revealed that low s-CD95L concentrations [<516 pg/mL, HR, 3.54; 95% confidence interval (CI), 1.13–11.11), and <1,200 activated CD8+ (Granzyme B+) cells (HR, 2.63; 95% CI, 1.16–5.95) were independent poor prognostic factors for recurrence, whereas >6,000 CD3+ cells (HR, 0.34; 95% CI, 0.15–0.79) was a good prognostic factor. Thus, low levels of s-CD95L (<516 pg/mL) are correlated with lower numbers of tumor-infiltrating lymphocytes (CD3+ and CD8+, and also CD4 and FoxP3 T cells) in advanced HGSOC and are a poor prognostic marker. Implications: Serum s-CD95L is correlated with a number of tumor-infiltrating immune cells in HGSOC and could be used as a noninvasive marker of tumor immune infiltration to select patients referred for immunotherapy trials that evaluate checkpoint inhibitor treatment.
@article{de_la_motte_rouge_serum_2019,
	title = {Serum {CD95L} {Level} {Correlates} with {Tumor} {Immune} {Infiltration} and {Is} a {Positive} {Prognostic} {Marker} for {Advanced} {High}-{Grade} {Serous} {Ovarian} {Cancer}},
	volume = {17},
	issn = {1541-7786, 1557-3125},
	url = {https://aacrjournals.org/mcr/article/17/12/2537/269266/Serum-CD95L-Level-Correlates-with-Tumor-Immune},
	doi = {10.1158/1541-7786.MCR-19-0449},
	abstract = {Abstract
            
              
              Soluble CD95L (s-CD95L) is a chemoattractant for certain lymphocyte subpopulations. We examined whether this ligand is a prognostic marker for high-grade serous ovarian cancer (HGSOC) and whether it is associated with accumulation of immune cells in the tumor. Serum s-CD95L levels in 51 patients with advanced ovarian cancer were tested by ELISA. IHC staining of CD3, CD4, CD8, CD20, CD163, CD31, FoxP3, CCR6, IL-17, Granzyme B, PD-L1, and membrane CD95L was used to assess tumor-infiltrating immune cells. Although the intensity of CD3, CD8, CD4, CD20, and CD163 in tumor tissues remained constant regardless of membrane CD95L expression, tumors in patients with HGSOC with s-CD95L levels ≥516 pg/mL showed increased infiltration by CD3+ T cells (P = 0.001), comprising both cytotoxic CD8+ (P = 0.01) and CD4+ (P = 0.0062) cells including FoxP3+ regulatory T cells (P = 0.0044). Also, the number of tumor-infiltrating CD20+ B cells (P = 0.0094) increased in these patients. Multivariate analyses revealed that low s-CD95L concentrations [\&lt;516 pg/mL, HR, 3.54; 95\% confidence interval (CI), 1.13–11.11), and \&lt;1,200 activated CD8+ (Granzyme B+) cells (HR, 2.63; 95\% CI, 1.16–5.95) were independent poor prognostic factors for recurrence, whereas \&gt;6,000 CD3+ cells (HR, 0.34; 95\% CI, 0.15–0.79) was a good prognostic factor. Thus, low levels of s-CD95L (\&lt;516 pg/mL) are correlated with lower numbers of tumor-infiltrating lymphocytes (CD3+ and CD8+, and also CD4 and FoxP3 T cells) in advanced HGSOC and are a poor prognostic marker.
            
            
              Implications:
              Serum s-CD95L is correlated with a number of tumor-infiltrating immune cells in HGSOC and could be used as a noninvasive marker of tumor immune infiltration to select patients referred for immunotherapy trials that evaluate checkpoint inhibitor treatment.},
	language = {en},
	number = {12},
	urldate = {2024-04-03},
	journal = {Molecular Cancer Research},
	author = {De La Motte Rouge, Thibault and Corné, Julien and Cauchois, Aurélie and Le Boulch, Marie and Poupon, Clotilde and Henno, Sébastien and Rioux-Leclercq, Nathalie and Le Pabic, Estelle and Laviolle, Bruno and Catros, Véronique and Levêque, Jean and Fautrel, Alain and Le Gallo, Matthieu and Legembre, Patrick and Lavoué, Vincent},
	month = dec,
	year = {2019},
	pages = {2537--2548},
	file = {De La Motte Rouge et al. - 2019 - Serum CD95L Level Correlates with Tumor Immune Inf.pdf:D\:\\Home\\maguillout\\Zotero\\Donnees\\storage\\RL4Y29Y7\\De La Motte Rouge et al. - 2019 - Serum CD95L Level Correlates with Tumor Immune Inf.pdf:application/pdf},
}
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