Dynamic change of immune-related gene expression status during chemoradiotherapy in locally advanced esophageal cancer

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Presenters

Takuro Mizukami

Citation

Annals of Oncology (2018) 29 (suppl_8): viii649-viii669. 10.1093/annonc/mdy303

Authors

T. Mizukami1, Y. Sunakawa1, H. Arai1, M. Chosokabe2, A. Doi1, Y. Horie1, M. Hirakawa1, O. Saji3, S. Naruki2, N. Izawa1, T. Ogura1, T. Tsuda1, T. Enomoto3, S. Mikami3, T. Fujino2, T. Otsubo3, T.E. Nakajima1

Author affiliations

  • 1 Clinical Oncology, St. Marianna University School of Medicine, 2168511 - Kanagawa/JP
  • 2 Pathology, St.Marianna University School of Medicine, 216-8511 - Kanagawa/JP
  • 3 Gastroenterological And General Surgery, St. Marianna University School of Medicine, 2168511 - Kanagawa/JP
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Resources

Background

Either chemotherapy or radiotherapy is standard of care for esophageal cancer (EC), and they are known to offer enhancement of both tumor and host immune system [B Park, et al. Int J Mol Sci 2014; Emens LA, et al. Cancer Immunol Res 2015]. However, there are few reports regarding the impact of chemoradiotherapy (CRT) on the tumor immunity.

Methods

We retrospectively examined patients (pts) with available tumor samples at 2 points (pre- and post-treatment) among EC pts who received chemotherapy with platinum and/or radiation in our institute between 2010 and 2015. Immunohistochemistry (IHC) staining for the samples was performed and the positivity of PD-L1 was determined as score >1 of the Allred methods. In addition, expression levels of immune-related genes were analyzed using HTG EdgeSeq Immuno-Oncology Assay (HTG Molecular Diagnostics, Inc., Tucson, United States).

Results

Eighty-four pts were evaluable (median age of 68yrs, 88% male, 7%/9%/34%/48%/1% for primary tumor of Ce/Ut/Mt/Lt/Ae, 12%/19%/52%/17% for Stage I/II/III/IV, 95% squamous cell carcinoma, 48%/52% pts treated with chemotherapy/CRT). Frequency of PD-L1 IHC expression was higher in the samples after chemotherapy compared in those before chemotherapy (14% to 36%), while it was lower in the samples after CRT compared in those after CRT (13% to 7%). There was a significant difference in the positive rate at post-treatment between chemotherapy and CRT (P = 0.01). Comprehensive analysis to compare gene expression levels of immune-related genes between pre- and post-treatment found 17 up-regulated and 34 down-regulated genes in pts treated with CRT. Specially, IL18, GZMA, and SPINK5 genes were identified for elevated genes, while PDGFRB, TNFRSF12A, and ITGB1 genes for degraded genes.

Conclusions

Positivity of PD-L1 was different after the treatment between in EC pts receiving chemotherapy and in those receiving CRT. Genes related to inflammatory response and angiogenesis may contribute to the change of tumor immune status by CRT in EC.

Clinical trial identification

Legal entity responsible for the study

Takako Eguchi Nakajima.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

T.E. Nakajima: Personal financial interests: Eli Lilly, Sanofi, Chugai, Sawai, Bayer, BMS, Taiho, Merck, Ono, Takeda, Mochida, MSD; Institutional financial interests: Ono, Taiho, A2 Health Care, JCRO, Daiichi-Sankyo, Mediscience Planning. All other authors have declared no conflicts of interest.

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