A Study of the Tumor Microenvironment Affecting the Efficacy of Immunotherapy for Esophageal Cancer

Esophageal Cancer Clinical Trial

Official title:

A Study of the Tumor Microenvironment Affecting the Efficacy of Immunotherapy for Esophageal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06219031
• Other study ID #: WDRY2024-K007
• Status: Completed
• Start date: December 1, 2023
• Est. completion date: January 1, 2024

Study information

• Verified date: January 2024
• Source: Renmin Hospital of Wuhan University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study is a retrospective study of clinical specimens. The study subjects were patients with esophageal cancer who received immunotherapy. Tumor tissue specimens surgically removed from patients before treatment will be collected primarily. In situ immunohistochemistry and multicolor immunofluorescence will be performed. We hypothesize that there are differences in lipid metabolism-related proteins in tumor tissues and immune cells in the preexisting tumor microenvironment in patients with esophageal cancer prior to immunotherapy, and that there is a link between such differences and the efficacy of immunotherapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: January 1, 2024
• Est. primary completion date: December 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Esophageal cancer patients receiving immunotherapy

2. Radical esophagectomy for esophageal cancer at our institution prior to receiving immunotherapy

3. Age greater than or equal to 18 years and less than or equal to 75 years old Imaging to assess patient efficacy after cycle 2 immunotherapy (CR/PR, SD/PD according to recist 1.1)

4. Pathology Tumor tissue available

Exclusion Criteria:

1. Clinical and pathologic information not available

2. Combined history of other malignant tumors

3. Unavailability of surgically resected tissue

4. Preoperative neoadjuvant therapy

5. Radical esophagectomy for esophageal cancer not performed prior to immunotherapy

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms

Intervention

Other:
• no intervention
no intervention

Locations

Country	Name	City	State
China	Renmin hosptial of Wuhan University	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
Renmin Hospital of Wuhan University

Country where clinical trial is conducted

China, 

References & Publications (14)

Arbore G, Albarello L, Bucci G, Punta M, Cossu A, Fanti L, Maurizio A, Di Mauro F, Bilello V, Arrigoni G, Bonfiglio S, Biancolini D, Puccetti F, Elmore U, Vago L, Cascinu S, Tonon G, Rosati R, Casorati G, Dellabona P. Preexisting Immunity Drives the Respo — View Citation

Fang P, Zhou J, Liang Z, Yang Y, Luan S, Xiao X, Li X, Zhang H, Shang Q, Zeng X, Yuan Y. Immunotherapy resistance in esophageal cancer: Possible mechanisms and clinical implications. Front Immunol. 2022 Sep 2;13:975986. doi: 10.3389/fimmu.2022.975986. eCo — View Citation

Gao L, Chen Y. A metabolomic and proteomic study to elucidate the molecular mechanisms of immunotherapy resistance in patients with oesophageal squamous cell carcinoma. Biomed Rep. 2023 Apr 6;18(5):36. doi: 10.3892/br.2023.1619. eCollection 2023 May. — View Citation

Koundouros N, Poulogiannis G. Reprogramming of fatty acid metabolism in cancer. Br J Cancer. 2020 Jan;122(1):4-22. doi: 10.1038/s41416-019-0650-z. Epub 2019 Dec 10. — View Citation

Lei X, Lei Y, Li JK, Du WX, Li RG, Yang J, Li J, Li F, Tan HB. Immune cells within the tumor microenvironment: Biological functions and roles in cancer immunotherapy. Cancer Lett. 2020 Feb 1;470:126-133. doi: 10.1016/j.canlet.2019.11.009. Epub 2019 Nov 12 — View Citation

Li Q, Liu T, Ding Z. Neoadjuvant immunotherapy for resectable esophageal cancer: A review. Front Immunol. 2022 Dec 8;13:1051841. doi: 10.3389/fimmu.2022.1051841. eCollection 2022. — View Citation

Lim SA, Wei J, Nguyen TM, Shi H, Su W, Palacios G, Dhungana Y, Chapman NM, Long L, Saravia J, Vogel P, Chi H. Lipid signalling enforces functional specialization of Treg cells in tumours. Nature. 2021 Mar;591(7849):306-311. doi: 10.1038/s41586-021-03235-6 — View Citation

Ma X, Bi E, Lu Y, Su P, Huang C, Liu L, Wang Q, Yang M, Kalady MF, Qian J, Zhang A, Gupte AA, Hamilton DJ, Zheng C, Yi Q. Cholesterol Induces CD8+ T Cell Exhaustion in the Tumor Microenvironment. Cell Metab. 2019 Jul 2;30(1):143-156.e5. doi: 10.1016/j.cme — View Citation

Parra ER, Zhang J, Jiang M, Tamegnon A, Pandurengan RK, Behrens C, Solis L, Haymaker C, Heymach JV, Moran C, Lee JJ, Gibbons D, Wistuba II. Immune cellular patterns of distribution affect outcomes of patients with non-small cell lung cancer. Nat Commun. 2 — View Citation

Su P, Wang Q, Bi E, Ma X, Liu L, Yang M, Qian J, Yi Q. Enhanced Lipid Accumulation and Metabolism Are Required for the Differentiation and Activation of Tumor-Associated Macrophages. Cancer Res. 2020 Apr 1;80(7):1438-1450. doi: 10.1158/0008-5472.CAN-19-29 — View Citation

Sung H, Ferlay J, Siegel RL, 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 May;71(3):209-249. doi: 10.3322/caa — View Citation

Xu C, Sun S, Johnson T, Qi R, Zhang S, Zhang J, Yang K. The glutathione peroxidase Gpx4 prevents lipid peroxidation and ferroptosis to sustain Treg cell activation and suppression of antitumor immunity. Cell Rep. 2021 Jun 15;35(11):109235. doi: 10.1016/j. — View Citation

Yang W, Bai Y, Xiong Y, Zhang J, Chen S, Zheng X, Meng X, Li L, Wang J, Xu C, Yan C, Wang L, Chang CC, Chang TY, Zhang T, Zhou P, Song BL, Liu W, Sun SC, Liu X, Li BL, Xu C. Potentiating the antitumour response of CD8(+) T cells by modulating cholesterol — View Citation

Yin J, Yuan J, Li Y, Fang Y, Wang R, Jiao H, Tang H, Zhang S, Lin S, Su F, Gu J, Jiang T, Lin D, Huang Z, Du C, Wu K, Tan L, Zhou Q. Neoadjuvant adebrelimab in locally advanced resectable esophageal squamous cell carcinoma: a phase 1b trial. Nat Med. 2023 — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immunotherapy efficacy	Imaging to assess patient efficacy after cycle 2 immunotherapy (CR/PR, SD/PD according to Recist 1.1)	2018-2022
Primary	CR?PR?SD?PD	CR:All target lesions disappear and the short diameter of all pathologic lymph nodes (both target and non-target nodes) must be reduced to <10 mm.; PR:At least 30% reduction in the sum of target lesion diameters from baseline levels SD:A relative increase in diameter sum of at least 20% (or the baseline value if the baseline measurement is minimal), referenced to the minimum of the sum of the diameters of all measured target lesions throughout the course of the experimental study; in addition to this, an increase in the absolute value of diameter sum of at least 5 mm must be met (the presence of one or more new lesions is also considered to be disease progression).; Translated with www.DeepL.com/Translator (free version) PD:The target lesion did not decrease to the level of PR, nor did it increase to the level of PD, and in between, the minimum value of the sum of the diameters can be used as a reference for the study.	2018-2022