Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jul 16;15(14):3641.
doi: 10.3390/cancers15143641.

A Potential Biomarker of Dynamic Change in Peripheral CD45RA-CD27+CD127+ Central Memory T Cells for Anti-PD-1 Therapy in Patients with Esophageal Squamous Cell Carcinoma

Mei Sakuma  1 , Kosaku Mimura  1   2 , Shotaro Nakajima  1 , Akinao Kaneta  1 , Tomohiro Kikuchi  1 , Azuma Nirei  1 , Takeshi Tada  1 , Hiroyuki Hanayama  1 , Hirokazu Okayama  1 , Wataru Sakamoto  1 , Motonobu Saito  1 , Tomoyuki Momma  1 , Zenichiro Saze  1 , Koji Kono  1
Affiliations

A Potential Biomarker of Dynamic Change in Peripheral CD45RA-CD27+CD127+ Central Memory T Cells for Anti-PD-1 Therapy in Patients with Esophageal Squamous Cell Carcinoma

Mei Sakuma et al. Cancers (Basel). .

Abstract

In order to develop a biomarker predicting the efficacy of treatments for patients with esophageal squamous cell carcinoma (ESCC), we evaluated the subpopulation of T cells in ESCC patients treated with chemotherapy (CT), chemoradiotherapy (CRT), and nivolumab therapy (NT). Fifty-five ESCC patients were enrolled in this study, and peripheral blood samples were collected before and after CT or CRT and during NT. Frequencies of memory, differentiated, and exhausted T cells were evaluated using flow cytometry among cStages, treatment strategies, pathological responses of CT/CRT, and during NT. The frequencies of PD-1+ or TIM-3+CD4+ T cells were significantly higher in patients with cStage IV. PD-1+CD4+ and TIM-3+CD8+ T-cell populations were significantly higher in patients treated with CRT but were not associated with treatment response. The frequencies of both CD4+ and CD8+ CD45RA-CD27+CD127+ central memory T cells (TCM) were significantly decreased during the course of NT in the progressive disease group. Taken together, the alteration in frequency of CD45RA-CD27+CD127+ TCM during NT may be a biomarker to predict its therapeutic response in ESCC patients.

Keywords: PD-1; TIM-3; biomarker; central memory T cell; esophageal squamous cell carcinoma.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The frequency of each T-cell subset was compared at different cStages. Frequencies of memory T cells (TCM and TEM), differentiated T cells (Tdiff) (a), and exhausted T cells (b) were evaluated among cStages in all enrolled patients. * p < 0.05, ** p < 0.01, *** p < 0.001.
Figure 2
Figure 2
The frequency of each T-cell subset was compared for different treatment strategies. cStage I patients did not receive neoadjuvant therapy before blood collection and were therefore classified as the non-treatment group in this analysis. Frequencies of memory T cells (TCM and TEM), differentiated T cells (Tdiff) (a), and exhausted T cells (b) were evaluated among treatment strategies in all enrolled patients. * p < 0.05, ** p < 0.01, *** p < 0.001.
Figure 3
Figure 3
The frequency of each T-cell subset was compared in response to neoadjuvant CT or CRT. The response to neoadjuvant therapy was classified into grade 0–1a and 1b–3 groups, and all cStage II and III patients treated with neoadjuvant CT or CRT were enrolled in this analysis. Frequencies of memory T cells (TCM and TEM), differentiated T cells (Tdiff), and exhausted T cells were evaluated between the grade 0–1a and 1b–3 groups in each CT (a) and the CRT (b) group in eligible patients. * p < 0.05.
Figure 4
Figure 4
Comparison of each T-cell subset before (Pre) and after (Post) nivolumab therapy in the responder (partial response + stable disease) group and progressive disease (PD) group. Frequencies of memory T cells (TCM and TEM), differentiated T cells (Tdiff) (a), and exhausted T cells (b) were evaluated in all cStage IV patients who were treated with nivolumab therapy. * p < 0.05.
See this image and copyright information in PMC

References

    1. Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021;71:209–249. doi: 10.3322/caac.21660. - DOI - PubMed
    1. Watanabe M., Tachimori Y., Oyama T., Toh Y., Matsubara H., Ueno M., Kono K., Uno T., Ishihara R., Muro K., et al. Comprehensive registry of esophageal cancer in Japan, 2013. Esophagus. 2021;18:1–24. doi: 10.1007/s10388-020-00785-y. - DOI - PMC - PubMed
    1. Watanabe M., Otake R., Kozuki R., Toihata T., Takahashi K., Okamura A., Imamura Y. Recent progress in multidisciplinary treatment for patients with esophageal cancer. Surg. Today. 2020;50:12–20. doi: 10.1007/s00595-019-01878-7. - DOI - PMC - PubMed
    1. Hayashi K., Ando N., Watanabe H., Ide H., Nagai K., Aoyama N., Takiyama W., Ishida K., Isono K., Makuuchi H., et al. Phase II evaluation of protracted infusion of cisplatin and 5-fluorouracil in advanced squamous cell carcinoma of the esophagus: A Japan Esophageal Oncology Group (JEOG) Trial (JCOG9407) Jpn. J. Clin. Oncol. 2001;31:419–423. doi: 10.1093/jjco/hye090. - DOI - PubMed
    1. Hironaka S., Tsubosa Y., Mizusawa J., Kii T., Kato K., Tsushima T., Chin K., Tomori A., Okuno T., Taniki T., et al. Phase I/II trial of 2-weekly docetaxel combined with cisplatin plus fluorouracil in metastatic esophageal cancer (JCOG0807) Cancer Sci. 2014;105:1189–1195. doi: 10.1111/cas.12486. - DOI - PMC - PubMed