Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-848d4c4894-m9kch Total loading time: 0 Render date: 2024-04-30T14:53:11.298Z Has data issue: false hasContentIssue false

Chapter 59 - Immunotherapy for Gynaecological Cancers

from Section 12 - Miscellaneous

Published online by Cambridge University Press:  24 November 2021

By
Miguel Henriques Abreu  and
Marta Ferreira
Edited by
Tahir Mahmood ,
Charles Savona-Ventura ,
Ioannis Messinis  and
Sambit Mukhopadhyay
Tahir Mahmood
Affiliation:
Victoria Hospital, Kirkcaldy
Charles Savona-Ventura
Affiliation:
University of Malta, Malta
Ioannis Messinis
Affiliation:
University of Thessaly, Greece
Sambit Mukhopadhyay
Affiliation:
Norfolk & Norwich University Hospital, UK
Get access

Summary

Gynaecological cancers comprise a huge variety of tumours. In the three main organs (endometrium, cervix and ovary), tumours differ in biology and molecular features, explaining the differences in tumour behaviour. However, in all of them, effective treatment options for advanced disease are urgently needed. Immunotherapy could be one such strategy. The goal of immunotherapy is to promote antitumour immune responses by stimulating the host immune system, by enhancing immune response, by relieving immune suppression by the host immune system or by immunomodulation.

Until now, immune checkpoints inhibitors that modulate one of the most important pathways of tumour immune escape presented the most robust efficacy data, but many trials are still ongoing and are expected to provide important knowledge in the coming years.

In future, clinicians will be able to recognize immunotherapy toxicities early on and better deal with them, while appropriate patient selection for these therapeutics will allow a more personalized treatment approach.

Keywords

cancergynaecologyimmunotherapycervixovaryendometrium
Type
Chapter
Information
The EBCOG Postgraduate Textbook of Obstetrics & Gynaecology
Gynaecology
 , pp. 503 - 512
Publisher: Cambridge University Press
Print publication year: 2021

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Ventriglia, J, Paciolla, I, Pisano, C, et al. Immunotherapy in ovarian, endometrial and cervical cancer: state of the art and future perspectives. Cancer Treat Rev 2017;59:109–116.Google Scholar
Menderes, G, Schwab, CL, Black, J, Santin, AD. The role of the immune system in ovarian cancer and implications on therapy. Expert Rev Clin Immunol 2016;12:681–695.Google Scholar
Tse, BWC, Collins, A, Oehler, MK, Zippelius, A, Heinzelmann-Schwarz, VA. Antibody-based immunotherapy for ovarian cancer: where are we at? Ann Oncol 2014;15:322–331.CrossRefGoogle Scholar
Wefers, C, Lambert, LJ, Torensma, R, Hato, SV. Cellular immunotherapy in ovarian cancer: targeting the stem cell of recurrence. Gynecol Oncol 2015;137:335–342.Google Scholar
Zhang, L, Conejo-Garcia, JR, Katsaros, D, et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 2003;348:203–213.Google Scholar
Hwang, WT, Adams, SF, Tahirovic, E, et al. Prognostic significance of tumor-infiltrating T-cells in ovarian cancer: a meta-analysis. Gynecol Oncol 2012;124:192–198.CrossRefGoogle ScholarPubMed
Wang, W, Zou, W, Liu, JR. Tumor-infiltrating T cells in epithelial ovarian cancer: predictors of prognosis and biological basis of immunotherapy. Gynecol Oncol 2018;151:1–3CrossRefGoogle ScholarPubMed
Nelson, BH. New insights into tumor immunity revealed by the unique genetic and genomic aspects of ovarian cancer. Curr Opin Immunol 2015;33:93–100.Google Scholar
Liao, JB. Immunotherapy for gynecologic cancers. Gynecol Oncol 2016;142:3–5.Google Scholar
Bell, D, Berchuck, A, Birrer, M, et al. Integrated genomic analyses of ovarian cancer. Nature 2011;474:609–615.Google Scholar
Strickland, KC, Howitt, BE, Shukla, SA, et al. Association and prognostic significance of BRCA1/2–mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer. Oncotarget 2016;22:13587–13598.Google Scholar
Vanderstraeten, A, Tuyaerts, S, Amant, F. The immune system in the normal endometrium and implications for endometrial cancer development. J Reprod Immunol 2015;109:7–16.CrossRefGoogle ScholarPubMed
Wira, CR, Fahey, JV, Ghosh, M, et al. sex hormone regulation of innate immunity in the female reproductive tract. Am J Reprod Immunol 2010;63:544–565.CrossRefGoogle ScholarPubMed
Deligdisch, L. Morphologic correlates of host response in endometrial carcinoma. Am J R Immunol 1982;2:54–57.CrossRefGoogle ScholarPubMed
Silverberg, SG, Sasano, N, Yajima, A. Endometrial carcinoma in Miyagi Prefecture, Japan: histopathologicanalysis of a cancer registry-based series and comparison with cases in American women. Cancer 1982;49:1504–1510.Google Scholar
de Jong, RA, Leffers, N, Boezen, HM, et al. Presence of tumor-infiltrating lymphocytes is an independent prognostic factor in type I and II endometrial cancer. Gynecol Oncol 2009;114:105–110.CrossRefGoogle ScholarPubMed
Yamagami, W, Susumu, N, Tanaka, H, et al. Immunofluorescence-detected infiltration of CD4+FOXP3+ regulatory T cells is relevant to the prognosis of patients with endometrial cancer. Int J Gynecol Cancer 2011;21:1628–1634.Google Scholar
Kubler, K, Ayub, TH, Weber, SK, et al. Prognostic significance of tumor-associated macrophages in endometrial adenocarcinoma. Gynecol Oncol 2014;135:176–183.Google Scholar
Espinosa, I, Jose Carnicer, M, Catasus, L, et al. Myometrial invasion and lymph node metastasis in endometrioid carcinomas: tumor-associated macrophages, microvessel density, and HIF1A have a crucial role. Am J Pathol 2010;34:1708–1714.CrossRefGoogle ScholarPubMed
Alexandrov, LB, Nik-Zainal, S, Wedge, DC, et al. Signatures of mutational processes in human cancer. Nature 2013;500:415–421.Google Scholar
Herrero, R, Gonzalez, P, Markowitz, LE. Present status of human papillomavirus vaccine development and implementation. Lancet Oncol 2015;16:e206–e216.CrossRefGoogle ScholarPubMed
Lin, K, Roosinovich, E, Ma, B, Hung, CF, Wu, TC. Therapeutic HPV DNA vaccines. Immunol Res 2010;47:86–112.Google Scholar
Lee, SJ, Yang, A, Wu, TC, Hung, CF. Immunotherapy for human papillomavirus-associated disease and cervical cancer: review of clinical and translational research. Gynecol Oncol 2016;27: e51.Google Scholar
Trimble, CL, Morrow, MP, Kraynyak, KA, et al. Safety, efficacy and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomized, double blind, placebo-controlled phase 2b trial. Lancet 2015;386:2078–2088.Google Scholar
van der Burg, SH, Arens, R, Ossendorp, F, et al. Vaccines for established cancer: overcoming the challenges posed by immune evasion. Nat Rev Cancer 2016;16:219–233.Google Scholar
Van Poelgeest, MI, Welters, WM, van Esch, LF, et al. HPV16 synthetic long peptide (HPV16-SLP) vaccination therapy of patients with advanced or recurrent HPV16-induced gynecological carcinoma, a phase II trial. J Transl Med 2013;11:88.CrossRefGoogle ScholarPubMed
Smith, JB, Stashwick, C, Powell, DJ. B7-H4 as a potential target for immunotherapy for gynecologic cancers: a closer look. Gynecol Oncol 2014;134:181–189.CrossRefGoogle ScholarPubMed
Teng, MWL, Ngiow, SF, Ribas, A, Smyth, MJ. Classifying cancers based on T-cell infiltration and PD-L1. Cancer Res 2015;75:2139–2145.Google Scholar
Howitt, BE, Shukla, SA, Sholl, LM, et al. Association of polymerase e–mutated and microsatellite-instable endometrial cancers with neoantigen load, number of tumor-infiltrating lymphocytes, and expression of PD-1 and PD-L1. JAMA Oncol 2015;1:1319–1323.CrossRefGoogle ScholarPubMed
Herzog, TAD, Reddy, S. Gatalica ZPD- 1 and PD-L1 expression in 1599 gynecological malignancies: implications for immunotherapy. Gynecol Oncol 2015;137(Suppl. 1).Google Scholar
Le, DT, Uram, JN, Wang, H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 2015;372:2509–2520.CrossRefGoogle ScholarPubMed
Ott, PA, Bang, Y-J, Berton-Rigaud, D, et al. Safety and antitumor activity of pembrolizumab in advanced programmed death ligand 1-positive endometrial cancer: results from the KEYNOTE-028 study. J Clin Oncol 2017;35:2535–2541.Google Scholar
Menderes, G, Hicks, C, Black, JD, Schwab, CL, Santin, AD. Immune checkpoint inhibitors in gynecologic cancers with lessons learned from non-gynecologic cancers. Expert Opin Biol Ther 2016:16:989–1004.CrossRefGoogle ScholarPubMed
Bellone, S, Black, J, English, DP, et al. Solitomab, an EpCAM/CD3 bispecific antibody construct (BiTE), is highly active against primary uterine serous papillary carcinoma cell lines in vitro. Am J Obstet Gynecol 2016;214:99.e1–8.Google Scholar
Shaar, B, Krishnan, V, Tallapragada, S, Dorigo, O. Cell-based immunotherapy in gynecologic malignancies. Curr Opin Obstet Gynecol 2018;30:23–30.CrossRefGoogle Scholar
Stevanović, S, Draper, LM, Langhan, MM, et al. Complete regression of metastatic cervical cancer after treatment with human papillomavirus: targeted tumor-infiltrating T cells. J Clin Oncol 2015;33:1543–1550.Google Scholar
Haanen, JBAG, Carbonnel, F, Robert, C, et al. Management of toxicities from immunotherapy: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2018;29(Suppl. 4):iv264–iv266.Google Scholar
Hodi, FS, O’Day, SJ, McDermott, DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010;363:711–723.CrossRefGoogle ScholarPubMed
Weber, JS, Hodi, FS, Wolchok, JD, et al. Safety profile of nivolumab monotherapy: a pooled analysis of patients with advanced melanoma. J Clin Oncol 2017;35:785–792.Google Scholar
Reck, M, Rodriguez-Abreu, D, Robinson, AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 2016;375:1823–1833.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×