2,203
Views
11
CrossRef citations to date
0
Altmetric
Research Article

Deep immune profiling of ovarian tumors identifies minimal MHC-I expression after neoadjuvant chemotherapy as negatively associated with T-cell-dependent outcome

, , , , , , , , , , , , , , ORCID Icon & show all
Article: 1760705 | Received 25 Jul 2019, Accepted 30 Jan 2020, Published online: 13 May 2020

References

  • Vaughan S, Coward JI, Bast RCJ, Berchuck A, Berek JS, Brenton JD, Coukos G, Crum CC, Drapkin R, Etemadmoghadam D, et al. Rethinking ovarian cancer: recommendations for improving outcomes. Nat Rev Cancer. 2011 Sep;11(10):719–12. doi:10.1038/nrc3144.
  • Leffers N, Gooden MJM, de Jong RA, Hoogeboom B-N, Ten Hoor KA, Hollema H, Boezen HM, van der Zee AGJ, Daemen T, Nijman HW, et al. Prognostic significance of tumor-infiltrating T-lymphocytes in primary and metastatic lesions of advanced stage ovarian cancer. Cancer Immunol Immunother. 2009 Mar;58(3):449–459. doi:10.1007/s00262-008-0583-5.
  • Vermeij R, de Bock GH, Leffers N, Ten Hoor KA, Schulze U, Hollema H, van der Burg SH, van der Zee AGJ, Daemen T, Nijman HW, et al. Tumor-infiltrating cytotoxic T lymphocytes as independent prognostic factor in epithelial ovarian cancer with wilms tumor protein 1 overexpression. J Immunother. 2011;34(6):516–523. doi:10.1097/CJI.0b013e31821e012f.
  • Hwang W-T, Adams SF, Tahirovic E, Hagemann IS, Coukos G. Prognostic significance of tumor-infiltrating T cells in ovarian cancer: a meta-analysis. Gynecol Oncol. 2012 Feb;124(2):192–198. doi:10.1016/j.ygyno.2011.09.039.
  • Barnes TA, Amir E. HYPE or HOPE: the prognostic value of infiltrating immune cells in cancer. Br J Cancer. 2018 Jan;118(2):e5. doi:10.1038/bjc.2017.417.
  • Nelson BH. The impact of T-cell immunity on ovarian cancer outcomes. Immunol Rev. 2008 Apr;222:101–116. doi:10.1111/j.1600-065X.2008.00614.x.
  • Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, Jungbluth AA, Frosina D, Gnjatic S, Ambrosone C, et al. Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci U S A. 2005 Dec;102(51):18538–18543. doi:10.1073/pnas.0509182102.
  • Wouters MCA, Komdeur FL, Workel HH, Klip HG, Plat A, Kooi NM, Wisman GBA, Mourits MJE, Arts HJG, Oonk MHM, et al. Treatment regimen, surgical outcome, and T-cell differentiation influence prognostic benefit of tumor-infiltrating lymphocytes in high-grade serous ovarian cancer. Clin Cancer Res. 2016 Feb;22(3):714–724. doi:10.1158/1078-0432.CCR-15-1617.
  • Wouters MCA, Komdeur FL, de Bruyn M, Nijman HW. Size matters: survival benefit conferred by intratumoral T cells is dependent on surgical outcome, treatment sequence and T cell differentiation. Oncoimmunology. 2016 5;May(5):e1122863. doi:10.1080/2162402X.2015.1122863.
  • Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJM, Robert L, Chmielowski B, Spasic M, Henry G, Ciobanu V, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014 Nov;515(7528):568–571. doi:10.1038/nature13954.
  • Karyampudi L, Lamichhane P, Krempski J, Kalli KR, Behrens MD, Vargas DM, Hartmann LC, Janco JMT, Dong H, Hedin KE, et al. PD-1 blunts the function of ovarian tumor-infiltrating dendritic cells by inactivating NF-kappaB. Cancer Res. 2016 Jan;76(2):239–250. doi:10.1158/0008-5472.CAN-15-0748.
  • Landskron J, Helland O, Torgersen KM, Aandahl EM, Gjertsen BT, Bjorge L, Taskén K. Activated regulatory and memory T-cells accumulate in malignant ascites from ovarian carcinoma patients. Cancer Immunol Immunother. 2015 Mar;64(3):337–347. doi:10.1007/s00262-014-1636-6.
  • Teng MWL, Ngiow SF, Ribas A, Smyth MJ. Classifying cancers based on T-cell infiltration and PD-L1. Cancer Res. 2015 Jun;75(11):2139–2145. doi:10.1158/0008-5472.CAN-15-0255.
  • Khagi Y, Kurzrock R, Patel SP. Next generation predictive biomarkers for immune checkpoint inhibition. Cancer Metastasis Rev. 2017 Mar;36(1):179–190. doi:10.1007/s10555-016-9652-y.
  • Wang D, Guo L, Wu X. Checkpoint inhibitors in immunotherapy of ovarian cancer. Tumour Biol. 2015 Jan;36(1):33–39. doi:10.1007/s13277-014-2848-2.
  • Komdeur FL, Wouters MCA, Workel HH, Tijans AM, Terwindt ALJ, Brunekreeft KL, Plat A, Klip HG, Eggink FA, Leffers N et al. CD103+ intraepithelial T cells in high-grade serous ovarian cancer are phenotypically diverse TCRalphabeta+ CD8alphabeta+ T cells that can be targeted for cancer immunotherapy. Oncotarget. 2016 Nov;7(46):75130–75144. doi:10.18632/oncotarget.12077.
  • Lo CS, Sanii S, Kroeger DR, Milne K, Talhouk A, Chiu DS, Rahimi K, Shaw PA, Clarke BA, Nelson BH, et al. Neoadjuvant chemotherapy of ovarian cancer results in three patterns of tumor-infiltrating lymphocyte response with distinct implications for immunotherapy. Clin Cancer Res. 2017 Feb;23(4):925–934. doi:10.1158/1078-0432.CCR-16-1433.
  • Romero P, Zippelius A, Kurth I, Pittet MJ, Touvrey C, Iancu EM, Corthesy P, Devevre E, Speiser DE, Rufer N, et al. Four functionally distinct populations of human effector-memory CD8 + T lymphocytes. J Immunol. 2007 Apr;178(7):4112–4119. doi:10.4049/jimmunol.178.7.4112.
  • Workel HH, Lubbers JM, Arnold R, Prins TM, van der Vlies P, de Lange K, Bosse T, van Gool IC, Eggink FA, Wouters MCA, et al. A transcriptionally distinct CXCL13þCD103þCD8þ T-cell population is associated with B-cell recruitment and neoantigen load in human cancer. Cancer Immunol Res. 2019;7(5):784–796. doi:10.1158/2326-6066.CIR-18-0517.
  • Mesnage SJL, Auguste A, Genestie C, Dunant A, Pain E, Drusch F, Gouy S, Morice P, Bentivegna E, Lhomme C, et al. Neoadjuvant chemotherapy (NACT) increases immune infiltration and programmed death-ligand 1 (PD-L1) expression in epithelial ovarian cancer (EOC). Ann Oncol Off J Eur Soc Med Oncol. 2017 Mar;28(3):651–657. doi:10.1093/annonc/mdw625.
  • Polcher M, Braun M, Friedrichs N, Rudlowski C, Bercht E, Fimmers R, Sauerwald A, Keyver-Paik M-D, Kübler K, Büttner R, et al. Foxp3+ cell infiltration and granzyme B+/Foxp3+ cell ratio are associated with outcome in neoadjuvant chemotherapy-treated ovarian carcinoma. Cancer Immunol Immunother. 2010 Jun;59(6):909–919. doi:10.1007/s00262-010-0817-1.
  • Eggink FA, Mom CH, Kruitwagen RF, Reyners AK, Van Driel WJ, Massuger LF, Niemeijer GC, Van der Zee AG, Van der Aa MA, Nijman HW, et al. Improved outcomes due to changes in organization of care for patients with ovarian cancer in the Netherlands. Gynecol Oncol [Internet]. 2016 Jun 1;141(3):524–530. [cited 2019 Apr 4]. https://www.sciencedirect.com/science/article/pii/S0090825816301408.
  • Scott GD, Atwater SK, Gratzinger DA. Normative data for flow cytometry immunophenotyping of benign lymph nodes sampled by surgical biopsy. J Clin Pathol [Internet]. 2018 Feb;71(2):174–179. [cited 2019 Apr 3]. http://jcp.bmj.com/lookup/doi/10.1136/jclinpath-2017-204687.
  • Tedla N, Dwyer J, Truskett P, Taub D, Wakefield D, Lloyd A. Phenotypic and functional characterization of lymphocytes derived from normal and HIV-1-infected human lymph nodes. Clin Exp Immunol [Internet]. 1999 Jul;117(1):92–99. [cited 2019 Apr 3]. http://www.ncbi.nlm.nih.gov/pubmed/10403921.
  • Heeren AM, Koster BD, Samuels S, Ferns DM, Chondronasiou D, Kenter GG, Jordanova ES, de Gruijl TD. High and interrelated rates of PD-L1+CD14+ antigen-presenting cells and regulatory T cells mark the microenvironment of metastatic lymph nodes from patients with cervical cancer. Cancer Immunol Res [Internet]. 2015 Jan 1;3(1):48–58. [cited 2019 Apr 3]. http://www.ncbi.nlm.nih.gov/pubmed/25361854.
  • Dillman RO, Cornforth AN, Nistor GI, McClay EF, Amatruda TT, Depriest C. Randomized phase II trial of autologous dendritic cell vaccines versus autologous tumor cell vaccines in metastatic melanoma: 5-year follow up and additional analyses. J Immunother Cancer [Internet]. 2018 Dec 6;6(1):19. [cited 2019 Apr 3]. http://www.ncbi.nlm.nih.gov/pubmed/29510745.
  • Martin Lluesma S, Wolfer A, Harari A, Kandalaft LE. Cancer vaccines in ovarian cancer: how can we improve? Biomedicines [Internet]. 2016 May 3;4(2):10. [cited 2019 Apr 3]. http://www.mdpi.com/2227-9059/4/2/10.
  • Wu X, Feng Q-M, Wang Y, Shi J, Ge H-L, Di W. The immunologic aspects in advanced ovarian cancer patients treated with paclitaxel and carboplatin chemotherapy. Cancer Immunol Immunother. 2010 Feb;59(2):279–291. doi:10.1007/s00262-009-0749-9.
  • Wu Y, Xiab R, Dai C, Yan S, Xie T, Liu B, Gan L, Zhuang Z, Huang Q. Dexamethasone inhibits the proliferation of tumor cells. Cancer Manag Res [Internet]. 2019 Feb;11:1141–1154. [cited 2019 Apr 4]. http://www.ncbi.nlm.nih.gov/pubmed/30774442.
  • Corcoran T, Paech M, Law D, Muchatuta NA, French M, Ho KM. Intraoperative dexamethasone alters immune cell populations in patients undergoing elective laparoscopic gynaecological surgery. Br J Anaesth [Internet]. 2017 Aug 1;119(2):221–230. [cited 2019 Apr 4]. http://www.ncbi.nlm.nih.gov/pubmed/28854534.
  • Komdeur FL, Prins TM, van de Wall S, Plat A, Wisman GBA, Hollema H, Daemen T, Church DN, de Bruyn M, Nijman HW, et al. CD103+ tumor-infiltrating lymphocytes are tumor-reactive intraepithelial CD8+ T cells associated with prognostic benefit and therapy response in cervical cancer. Oncoimmunology. 2017;6(9):e1338230. doi:10.1080/2162402X.2017.1338230.
  • Welters MJ, van der Sluis TC, van Meir H, Loof NM, van Ham VJ, van Duikeren S, Santegoets SJ, Arens R, de Kam ML, Cohen AF, et al. Vaccination during myeloid cell depletion by cancer chemotherapy fosters robust T cell responses. Sci Transl Med. 2016 Apr;8(334):334ra52. doi:10.1126/scitranslmed.aad8307.
  • Polk A, Svane I-M, Andersson M, Nielsen D. Checkpoint inhibitors in breast cancer - Current status. Cancer Treat Rev. 2018 Feb;63:122–134. doi:10.1016/j.ctrv.2017.12.008.
  • Adams S, Diamond JR, Hamilton E, Pohlmann PR, Tolaney SM, Chang C-W, Zhang W, Iizuka K, Foster PG, Molinero L, et al. Atezolizumab plus nab-paclitaxel in the treatment of metastatic triple-negative breast cancer with 2-year survival follow-up. JAMA Oncol [Internet]. 2019 Mar 1;5(3):334. [cited 2019 Apr 3]. http://www.ncbi.nlm.nih.gov/pubmed/30347025.
  • Nanda R, Liu MC, Yau C, Asare S, Hylton N, Veer LV, Perlmutter J, Wallace AM, Chien AJ, Forero-Torres A, et al. Pembrolizumab plus standard neoadjuvant therapy for high-risk breast cancer (BC): results from I-SPY 2. J Clin Oncol [Internet]. 2017 May 20;35(15_suppl):506. [cited 2019 Apr 3]. doi:10.1200/JCO.2017.35.15_suppl.506.
  • Arce Vargas F, Furness AJS, Litchfield K, Joshi K, Rosenthal R, Ghorani E, Solomon I, Lesko MH, Ruef N, Roddie C, et al. Fc effector function contributes to the activity of human anti-CTLA-4 antibodies. Cancer Cell [Internet]. 2018 Apr 9;33(4):649–663.e4. [cited 2019 Apr 3]. http://www.ncbi.nlm.nih.gov/pubmed/29576375.
  • Conrad C, Gregorio J, Wang Y-H, Ito T, Meller S, Hanabuchi S, Anderson S, Atkinson N, Ramirez PT, Liu Y-J, et al. Plasmacytoid dendritic cells promote immunosuppression in ovarian cancer via ICOS costimulation of Foxp3(+) T-regulatory cells. Cancer Res [Internet]. 2012 Oct 15;72(20):5240–5249. [cited 2019 Apr 3]. http://www.ncbi.nlm.nih.gov/pubmed/22850422.
  • Toker A, Nguyen LT, Stone SC, Yang SYC, Katz SR, Shaw PA, Clarke BA, Ghazarian D, Al-Habeeb A, Easson A, et al. Regulatory T cells in ovarian cancer are characterized by a highly activated phenotype distinct from that in melanoma. Clin Cancer Res [Internet]. 2018 Nov 15;24(22):5685–5696. [cited 2019 Apr 3]. http://clincancerres.aacrjournals.org/lookup/doi/10.1158/1078-0432.CCR-18-0554.
  • Johnson DB, Peng C, Sosman JA. Nivolumab in melanoma: latest evidence and clinical potential. Ther Adv Med Oncol [Internet]. 2015 Mar;7(2):97–106. [cited 2019 Apr 3]. http://www.ncbi.nlm.nih.gov/pubmed/25755682.
  • Varga A, Piha-Paul SA, Ott PA, Mehnert JM, Berton-Rigaud D, Johnson EA, Cheng JD, Yuan S, Rubin EH, Matei DE, et al. Antitumor activity and safety of pembrolizumab in patients (pts) with PD-L1 positive advanced ovarian cancer: interim results from a phase Ib study. J Clin Oncol [Internet]. 2015 May 20;33(15_suppl):5510. [cited 2019 Apr 3]. http://ascopubs.org/doi/10.1200/jco.2015.33.15_suppl.5510.
  • Hamanishi J, Mandai M, Ikeda T, Minami M, Kawaguchi A, Murayama T, Kanai M, Mori Y, Matsumoto S, Chikuma S, et al. Safety and antitumor activity of anti–PD-1 antibody, nivolumab, in patients with platinum-resistant ovarian cancer. J Clin Oncol [Internet]. 2015 Dec 1;33(34):4015–4022. [cited 2019 Apr 3]. http://www.ncbi.nlm.nih.gov/pubmed/26351349.
  • Burr ML, Sparbier CE, Chan KL, Chan Y-C, Kersbergen A, Lam EYN, Azidis-Yates E, Vassiliadis D, Bell CC, Gilan O, et al. An evolutionarily conserved function of polycomb silences the MHC Class I antigen presentation pathway and enables immune evasion in cancer. Cancer Cell [Internet]. 2019 Oct 14;36(4):385–401.e8. [cited 2019 Oct 23]. http://www.ncbi.nlm.nih.gov/pubmed/31564637.
  • Luo N, Nixon MJ, Gonzalez-Ericsson PI, Sanchez V, Opalenik SR, Li H, Zahnow CA, Nickels ML, Liu F, Tantawy MN, et al. DNA methyltransferase inhibition upregulates MHC-I to potentiate cytotoxic T lymphocyte responses in breast cancer. Nat Commun [Internet]. 2018;9(1):1–11. doi:10.1038/s41467-017-02630-w.