Immunological and molecular features of the tumor microenvironment of long-term survivors of ovarian cancer

被引：2

作者：

Nelson, Brad H. ^{[1
,2
,3
]}

Hamilton, Phineas ^{[1
]}

Minh Tung Phung ^{[4
,5
]}

Milne, Katy ^{[1
]}

Harris, Bronwyn ^{[1
]}

Thornton, Shelby

Stevens, Donald ^{[1
]}

Kalaria, Shreena ^{[2
]}

Singh, Karanvir ^{[1
]}

Laumont, Celine M. ^{[1
,3
]}

Moss, Elena ^{[1
]}

Alimujiang, Aliya ^{[4
]}

Meagher, Nicola S. ^{[6
,7
]}

Bolithon, Adelyn ^{[6
,8
]}

Fereday, Sian ^{[9
,10
]}

Kennedy, Catherine J. ^{[11
,12
,13
]}

Hendley, Joy ^{[9
]}

Ariyaratne, Dinuka ^{[9
]}

Alsop, Kathryn ^{[9
,10
]}

Traficante, Nadia ^{[9
,11
]}

Goode, Ellen L. ^{[14
]}

Karnezis, Anthony ^{[15
]}

Shen, Hui ^{[16
]}

Richardson, Jean ^{[17
]}

McKinnonDeurloo, Cindy

Chase, Anne

Grout, Bronwyn

Doherty, Jennifer Anne ^{[18
]}

Harris, Holly R. ^{[19
,20
]}

Cushing-Haugen, Kara L. ^{[19
]}

Anglesio, Michael ^{[21
,22
,23
]}

Heinze, Karolin ^{[21
,22
,23
]}

Huntsman, David ^{[21
,24
]}

Talhouk, Aline ^{[21
,22
,23
]}

Hanley, Gillian E. ^{[21
,22
,23
]}

Alsop, Jennifer ^{[25
]}

Jimenez-Linan, Mercedes ^{[26
]}

Pharoah, Paul D. P. ^{[27
]}

Boros, Jessica ^{[11
,12
,13
]}

Brand, Alison H. ^{[12
,13
]}

Harnett, Paul R. ^{[13
,28
]}

Sharma, Raghwa ^{[13
,29
,30
]}

Hecht, Jonathan L. ^{[31
,32
]}

Sasamoto, Naoko ^{[32
,33
]}

Terry, Kathryn L. ^{[32
,33
,34
]}

Karlan, Beth ^{[35
]}

Lester, Jenny ^{[35
]}

Carney, Michael E. ^{[36
]}

Goodman, Marc T. ^{[37
]}

Hernandez, Brenda Y. ^{[38
]}

机构：

[1] BC Canc, Deeley Res Ctr, 2410 Lee Ave, Victoria, BC V8R 6V5, Canada

[2] Univ Victoria, Dept Biochem & Microbiol, Victoria, BC, Canada

[3] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada

[4] Univ Michigan, Sch Publ Hlth, 1415 Washington Hts, Ann Arbor, MI 48109 USA

[5] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA

[6] Univ NSW Sydney, Univ New South Wales NSW Med & Hlth, Sch Clin Med, Sydney, NSW, Australia

[7] Univ Sydney, Daffodil Ctr, Sydney, NSW, Australia

[8] Univ NSW Sydney, Lowy Canc Res Ctr, Adult Canc Program, Sydney, NSW, Australia

[9] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia

[10] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic, Australia

[11] Westmead Inst Med Res, Ctr Canc Res, Sydney, NSW, Australia

[12] Westmead Hosp, Dept Gynaecol Oncol, Sydney, NSW, Australia

[13] Univ Sydney, Fac Med & Hlth, Sydney, NSW, Australia

[14] Mayo Clin, Dept Quantitat Hlth Sci, Div Epidemiol, Rochester, MN USA

[15] Univ Calif Davis, Sch Med, Dept Pathol, Sacramento, CA 95817 USA

[16] Van Andel Inst, Grand Rapids, MI USA

[17] Univ Southern Calif, Keck Sch Med, Dept Populat & Publ Hlth Sci, Los Angeles, CA 90007 USA

[18] Univ Utah, Dept Populat Hlth Sci, Huntsman Canc Inst, Salt Lake City, UT USA

[19] Fred Hutchinson Canc Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA USA

[20] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA

[21] Univ British Columbia, Dept Obstet & Gynecol, Vancouver, BC, Canada

[22] Univ British Columbia, BC Canc, British Columbias Gynecol Canc Res Team OVCARE, Vancouver, BC, Canada

[23] Vancouver Gen Hosp, Vancouver, BC, Canada

[24] BC Canc Res Ctr, Dept Mol Oncol, Vancouver, BC, Canada

[25] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England

[26] Addenbrookes Hosp, Dept Histopathol, Cambridge, England

[27] Cedars Sinai Med Ctr, Dept Computat Biomed, West Hollywood, CA USA

[28] Westmead Hosp, NSW Hlth Pathol, Crown Princess Mary Canc Ctr, Sydney, NSW, Australia

[29] Westmead Hosp, NSW Hlth Pathol, Tissue Pathol & Diagnost Oncol, Sydney, NSW, Australia

[30] Western Sydney Univ, Sydney, NSW, Australia

[31] Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Brookline Ave, Boston, MA 02215 USA

[32] Harvard Med Sch, Boston, MA 02115 USA

[33] Brigham & Womens Hosp, Dept Obstet & Gynecol, Obstet & Gynecol Epidemiol Ctr, 75 Francis St, Boston, MA 02115 USA

[34] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[35] Univ Calif Los Angeles, Dept Obstet & Gynecol, David Geffen Sch Med, Los Angeles, CA 90024 USA

[36] Univ Hawaii, John A Burns Sch Med, Dept Obstet & Gynecol, Honolulu, HI 96822 USA

[37] Cedars Sinai Med Ctr, Canc Prevent & Control Program, Los Angeles, CA 90048 USA

[38] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA

[39] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany

[40] Canc Registry Norway, Res Dept, Oslo, Norway

[41] Friedrich Alexander Univ Erlangen Nurnberg, Dept Gynecol & Obstet, Comprehens Canc Ctr Erlangen EMN, Univ Hosp Erlangen, Erlangen, Germany

[42] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Gynecol & Obstet, Ribeirao Preto, Brazil

[43] Univ Calgary, Cumming Sch Med, Div Gynecol Oncol, Dept Oncol, Calgary, AB, Canada

[44] Univ Calgary, Foothills Med Ctr, Dept Pathol & Lab Med, Calgary, AB, Canada

[45] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA

[46] Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA

[47] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Div Gynecol Oncol, Pittsburgh, PA USA

[48] Magee Womens Res Inst, Womens Canc Res Ctr, Pittsburgh, PA USA

[49] Hillman Canc Ctr, Pittsburgh, PA USA

[50] Univ Colorado, Sch Publ Hlth, Epidemiol, Aurora, CO USA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2024年 / 134卷 / 24期

基金：

英国医学研究理事会; 美国国家卫生研究院; 加拿大健康研究院;

关键词：

INFILTRATING T-CELLS; FAVORABLE PROGNOSIS; GENE SIGNATURES; SUBTYPES; IMPACT; STROMA; LYMPHOCYTES; EXPRESSION; LANDSCAPE; MARKERS;

D O I：

10.1172/JCI179501

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

BACKGROUND. Despite an overall poor prognosis, about 15% of patients with advanced-stage tubo-ovarian high-grade serous carcinoma (HGSC) survive 10 or more years after standard treatment. METHODS. We evaluated the tumor microenvironment of this exceptional, understudied group using a large international cohort enriched for long-term survivors (LTS; 10+ years; n = 374) compared with mid-term (MTS; 5-7.99 years; n = 433) and short-term survivors (STS; 2-4.99 years; n = 416). Primary tumor samples were immunostained and scored for intraepithelial and intrastromal densities of 10 immune-cell subsets (including T cells, B cells, plasma cells, myeloid cells, PD-1(+) cells, and PD-L1(+) cells) and epithelial content. RESULTS. Positive associations with LTS compared with STS were seen for 9 of 10 immune-cell subsets. In particular, the combination of intraepithelial CD8(+) T cells and intrastromal B cells showed near 5-fold increased odds of LTS compared with STS. All of these associations were stronger in tumors with high epithelial content and/or the C4/Differentiated molecular subtype, despite immune-cell densities generally being higher in tumors with low epithelial content and/or the C2/Immunoreactive molecular subtype. CONCLUSION. The tumor microenvironment of HGSC LTS is distinguished by the intersection of T and B cell coinfiltration, high epithelial content, and C4/differentiated molecular subtype, features which may inspire new approaches to immunotherapy.

引用

页数：15

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