Prediction of treatment response from the microenvironment of tumor immunity in cervical cancer patients treated with chemoradiotherapy.
Adult
Aged
Aged, 80 and over
B7-H1 Antigen
/ genetics
CD8 Antigens
/ genetics
Chemoradiotherapy
DNA-Binding Proteins
/ genetics
Female
Forkhead Transcription Factors
/ genetics
Gene Expression Regulation, Neoplastic
Humans
Inflammation
Japan
Middle Aged
Prognosis
Retrospective Studies
Tumor Microenvironment
/ immunology
Uterine Cervical Neoplasms
/ genetics
CD8
CD8-based classification
Cervical cancer
Forkhead box P3
Human leukocyte antigen class I
Programmed death ligand 1
Radiotherapy
Tumor immunity
XRCC4
Journal
Medical molecular morphology
ISSN: 1860-1499
Titre abrégé: Med Mol Morphol
Pays: Japan
ID NLM: 101239023
Informations de publication
Date de publication:
Sep 2021
Sep 2021
Historique:
received:
24
02
2021
accepted:
29
04
2021
pubmed:
9
5
2021
medline:
13
1
2022
entrez:
8
5
2021
Statut:
ppublish
Résumé
To supplement clinical decision-making in the management of cervical cancer, various prognostic factors, including tumor immune microenvironments, were examined in patients with cervical cancer treated with definitive chemoradiotherapy. We retrospectively analyzed the expression of CD8, FoxP3, HLA-1, PD-L1, and XRCC4 in 100 cases of cervical cancer. The observed tumor immune microenvironments were also classified into three types: inflamed, excluded, and cold type. Less FoxP3+ T cells and cold-type tumor were found to be poor prognostic factors in addition to non-SCC, large pre-treatment tumor volume, and three or less cycles of concurrent chemotherapy based on multivariate analysis. Cold-type tumors had significantly worse prognoses than the other two types, whereas inflamed- and excluded-type tumors showed similar 5-year disease-specific survival (P < 0.001; 0% vs. 60.3% vs. 72.3%). Radiotherapy could overcome the inhibitory immune microenvironment that occurs in excluded type. Individualized combination therapy adapted to pre-treatment tumor immunity may be necessary to improve radiotherapy outcomes in cervical cancer.
Identifiants
pubmed: 33963949
doi: 10.1007/s00795-021-00290-w
pii: 10.1007/s00795-021-00290-w
doi:
Substances chimiques
B7-H1 Antigen
0
CD274 protein, human
0
CD8 Antigens
0
DNA-Binding Proteins
0
FOXP3 protein, human
0
Forkhead Transcription Factors
0
XRCC4 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
245-252Subventions
Organisme : Japan Society for the Promotion of Science
ID : 18K07760
Organisme : Japan Society for the Promotion of Science
ID : 18K07684
Informations de copyright
© 2021. The Japanese Society for Clinical Molecular Morphology.
Références
National Cancer Comprehensive Network 2020 NCCN guidelines: cervical cancer version 1. http://www.nccn.org/ . Accessed on 1 Jan 2021.
Pötter R, Haie-Meder C, Van Limbergen E, Barillot I, De Brabandere M, Dimopoulos J, GEC ESTRO Working Group et al (2006) Recommendations from gynaecological (GYN) GEC ESTRO working group (II): concepts and terms in 3D image-based treatment planning in cervix cancer brachytherapy-3D dose volume parameters and aspects of 3D image-based anatomy, radiation physics, radiobiology. Radiother Oncol 78:67–77. https://doi.org/10.1016/j.radonc.2005.11.014
doi: 10.1016/j.radonc.2005.11.014
Sturdza A, Pötter R, Fokdal LU, Haie-Meder C, Tan LT, Mazeron R et al (2016) Image guided brachytherapy in locally advanced cervical cancer: improved pelvic control and survival in RetroEMBRACE, a multicenter cohort study. Radiother Oncol 120:428–433. https://doi.org/10.1016/j.radonc.2016.03.011
doi: 10.1016/j.radonc.2016.03.011
pubmed: 27134181
Tanderup K, Fokdal LU, Sturdza A, Haie-Meder C, Mazeron R, van Limbergen E et al (2016) Effect of tumor dose, volume and overall treatment time on local control after radiochemotherapy including MRI guided brachytherapy of locally advanced cervical cancer. Radiother Oncol 120:441–446. https://doi.org/10.1016/j.radonc.2016.05.014
doi: 10.1016/j.radonc.2016.05.014
pubmed: 27350396
Takada Y, Someya M, Matsumoto Y, Satoh M, Nakata K, Hori M et al (2016) Influence of Ku86 and XRCC4 expression in uterine cervical cancer on the response to preoperative radiotherapy. Med Mol Morphol 49:210–216. https://doi.org/10.1007/s00795-016-0136-5
doi: 10.1007/s00795-016-0136-5
pubmed: 26867665
Tsuchiya T, Someya M, Takada Y, Hasegawa T, Kitagawa M, Fukushima Y et al (2020) Association between radiotherapy-induced alteration of programmed death ligand 1 and survival in patients with uterine cervical cancer undergoing preoperative radiotherapy. Strahlenther Onkol 196:725–735. https://doi.org/10.1007/s00066-019-01571-1
doi: 10.1007/s00066-019-01571-1
pubmed: 31953603
Someya M, Tsuchiya T, Fukushima Y, Hasegawa T, Takada Y, Hori M et al (2020) Association between cancer immunity and treatment results in uterine cervical cancer patients treated with radiotherapy. Jpn J Clin Oncol 50:1290–1297. https://doi.org/10.1093/jjco/hyaa149
doi: 10.1093/jjco/hyaa149
pubmed: 33089868
Camus M, Tosolini M, Mlecnik B, Pagès F, Kirilovsky A, Berger A et al (2009) Coordination of intratumoral immune reaction and human colorectal cancer recurrence. Cancer Res 69:2685–2693. https://doi.org/10.1158/0008-5472.CAN-08-2654
doi: 10.1158/0008-5472.CAN-08-2654
pubmed: 19258510
Galon J, Bruni D (2019) Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat Rev Drug Discov 18:197–218. https://doi.org/10.1038/s41573-018-0007-y
doi: 10.1038/s41573-018-0007-y
pubmed: 30610226
Suzuki Y, Mimura K, Yoshimoto Y, Watanabe M, Ohkubo Y, Izawa S et al (2012) Immunogenic tumor cell death induced by chemoradiotherapy in patients with esophageal squamous cell carcinoma. Cancer Res 72:3967–3976. https://doi.org/10.1158/0008-5472.CAN-12-0851
doi: 10.1158/0008-5472.CAN-12-0851
pubmed: 22700877
Someya M, Hasegawa T, Tsuchiya T, Kitagawa M, Gocho T, Fukushima Y et al (2020) Retrospective DVH analysis of point A based intracavitary brachytherapy for uterine cervical cancer. J Radiat Res 61:265–274. https://doi.org/10.1093/jrr/rrz099
doi: 10.1093/jrr/rrz099
pubmed: 32009177
pmcid: 7246069
Sakata K, Matsumoto Y, Tauchi H, Satoh M, Oouchi A, Nagakura H et al (2001) Expression of genes involved in repair of DNA double-strand breaks in normal and tumor tissues. Int J Radiat Oncol Biol Phys 49:161–167. https://doi.org/10.1016/s0360-3016(00)01352-3
doi: 10.1016/s0360-3016(00)01352-3
pubmed: 11163510
Rose PG, Java JJ, Whitney CW, Stehman FB, Lanciano R, Thomas GM (2014) Locally advanced adenocarcinoma and adenosquamous carcinomas of the cervix compared to squamous cell carcinomas of the cervix in gynecologic oncology group trials of cisplatin-based chemoradiation. Gynecol Oncol 135(2):208–212. https://doi.org/10.1016/j.ygyno.2014.08.018
doi: 10.1016/j.ygyno.2014.08.018
pubmed: 25152438
pmcid: 4557698
Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration (2008) Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials. J Clin Oncol 26(35):5802–5812. https://doi.org/10.1200/JCO.2008.16.4368
doi: 10.1200/JCO.2008.16.4368
pmcid: 2645100
Ho CK, Kornaga EN, Klimowicz AC, Enwere EK, Dean M, Bebb GD et al (2017) Expression of DNA damage response proteins in cervical cancer patients treated with radical chemoradiotherapy. Gynecol Oncol 145(1):176–184. https://doi.org/10.1016/j.ygyno.2016.12.025
doi: 10.1016/j.ygyno.2016.12.025
pubmed: 28131528
Shang B, Liu Y, Jiang SJ, Liu Y (2015) Prognostic value of tumor-infiltrating FoxP3+ regulatory T cells in cancers: a systematic review and meta-analysis. Sci Rep 14(5):15179. https://doi.org/10.1038/srep15179
doi: 10.1038/srep15179
Balermpas P, Martin D, Wieland U, Rave-Fränk M, Strebhardt K, Rödel C et al (2017) Human papilloma virus load and PD-1/PD-L1, CD8+ and FOXP3 in anal cancer patients treated with chemoradiotherapy: Rationale for immunotherapy. Oncoimmunology 6:e1288331. https://doi.org/10.1080/2162402X.2017.1288331
doi: 10.1080/2162402X.2017.1288331
pubmed: 28405521
pmcid: 5384387
Mlecnik B, Tosolini M, Kirilovsky A, Berger A, Bindea G, Meatchi T et al (2011) Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J Clin Oncol 29:610–618. https://doi.org/10.1200/JCO.2010.30.5425
doi: 10.1200/JCO.2010.30.5425
pubmed: 21245428
Mlecnik B, Bindea G, Angell HK, Maby P, Angelova M, Tougeron D et al (2016) Integrative analyses of colorectal cancer show immunoscore is a stronger predictor of patient survival than microsatellite instability. Immunity 44:698–711. https://doi.org/10.1016/j.immuni.2016.02.025
doi: 10.1016/j.immuni.2016.02.025
pubmed: 26982367
Martins PR, Machado CMT, Coxir SA, de Oliveira AJ, Moreira TB, Campos LS et al (2019) Cervical cancer patients that respond to chemoradiation therapy display an intense tumor infiltrating immune profile before treatment. Exp Mol Pathol 111:104314. https://doi.org/10.1016/j.yexmp.2019.104314
doi: 10.1016/j.yexmp.2019.104314
pubmed: 31654628
Chen H, Xia B, Zheng T, Lou G (2020) Immunoscore system combining CD8 and PD-1/PD-L1: a novel approach that predicts the clinical outcomes for cervical cancer. Int J Biol Markers 35:65–73. https://doi.org/10.1177/1724600819888771
doi: 10.1177/1724600819888771
pubmed: 31808707
Hellmann MD, Friedman CF, Wolchok JD (2016) Combinatorial cancer immunotherapies. Adv Immunol 130:251–277. https://doi.org/10.1016/bs.ai.2015.12.005
doi: 10.1016/bs.ai.2015.12.005
pubmed: 26923003
Demaria S, Coleman CN, Formenti SC (2016) Radiotherapy: changing the game in immunotherapy. Trends Cancer 2:286–294. https://doi.org/10.1016/j.trecan.2016.05.002
doi: 10.1016/j.trecan.2016.05.002
pubmed: 27774519
pmcid: 5070800
Hockel M, Schlenger K, Aral B, Mitze M, Schaffer U, Vaupel P (1996) Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Res 56:4509–4515
Hegde PS, Karanikas V, Evers S (2016) The where, the when, and the how of immune monitoring for cancer immunotherapies in the era of checkpoint inhibition. Clin Cancer Res 22:1865–1874. https://doi.org/10.1158/1078-0432.CCR-15-1507
doi: 10.1158/1078-0432.CCR-15-1507