Role of Cancer-associated Fibroblast, MDSCs and Immune Cell Interplays in the Resistance of Non-small Cell Lung Cancer to Anti-PD1/PD-L1 Therapies (COCKPI-T)

July 29, 2025 updated by: University Hospital, Bordeaux
Immunotherapy have revolutionized the field of oncology, but response rates are low and all patients relapse, due to cellular and soluble immunosuppressive mechanisms. These immunosuppressive mechanisms will be better characterized and their involvement in therapeutic responses in non-small cell lung cancers (NSCLC). Indeed, large transcriptomic analysis of different subsets of immunosuppressive cells will performed, correlating them to clinical outcome in a cohort of stage III disease, treated by radiochemotherapy and immunotherapy as maintenance, and stage IV treated by immunotherapy as first-line treatment. Furthermore, we will analyse cellular mechanisms by in vitro studies, assessing the effect of immunosuppressive cells, provided by fresh tumor samples, on phenotype and functions of lung cancer cell lines. The aim of this study is to better characterize immunosuppressive landscape of NSCLC and mechanisms involved in their protumor functions.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

In recent years, immune-based therapies have revolutionized the field of oncology by significantly improving survival of cancer patients. Despite sustained responses, only 20% to 40% of cancer patients respond. It has become clear that the immunosuppressive environment induced by tumor through cellular and/or soluble pathways critically contribute to hinder efficient antitumor immunity. The inhibition of these immunosuppressive networks thus represents an essential prerequisite for the improvement of responses to anticancer immunotherapies. Several immune and non -immune cell populations have been identified as key actors of tumor-induced immunosuppression, among which are myeloid-derived suppressor cells (MDSC), and cancer associated fibroblasts (CAF). However, in non-small cell lung cancers (NSCLC), the phenotypic characteristics and the prognostic role of these cells, the mechanisms underlying their immunosuppressive functions, and their role in dampening the efficacy of immunotherapies in clinical practice are less characterized. The aim of this project is to better characterize these different immunosuppressive subpopulations, and to study their role promoting NSCLC development and resistance to immunotherapies.

First the tumor CAF and immunosuppressive microenvironment using single cell RNA sequencing will be characterized (objective 1a). After identification of phenotypic markers, the immunosuppressive landscape of stage III NSCLC on a lung cancer cohort treated at Bordeaux University Hospital will be analysed, and data on CAF, MDSC and immune infiltration will be correlated with tumor characteristics and cancer outcome (objective 1b). Finally, the pro-tumor functions of CAF isolated from lung cancer patients will be assessed in vitro (objective 2).

Study Type

Observational

Enrollment (Estimated)

25

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients with lung carcinoma surgically treated by surgery only, or stage III lung carcinoma treated by concomitant radiochemotherapy followed by durvalumab (maintenance) treated between September 2018 and december 2021

Description

Inclusion Criteria:

  • consecutive patients
  • lung carcinoma surgically treated by surgery only (objectives 1a and 2), or stage III lung carcinoma treated by concomitant radiochemotherapy followed by durvalumab (maintenance) treated between September 2018 and december 2021 (objective 1b)

Exclusion Criteria:

  • patient receiving chemotherapy, radiotherapy or immunotherapy in the neoadjuvant setting (all objectives)
  • patient with previous cancer

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Prospective part of the study
Procedure: Tumor samples
Tumor samples will be collected by the pathologist at the reception of the tumor removed during surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Descriptive analysis of immune infiltration and phenotypic and functional characteristics of the different cell subgroups isolated from fresh tumors
Time Frame: At the time of surgery only, when fresh tumor is resected
Exploratory analysis of the immune infiltration (phenotype and function of immunosuppressive and antitumor immune cells) and of the cancer-associated fibroblasts through a transcriptomic analysis of fresh resected lung carcinoma, comparing patients with lymph node involvement or not. Bioinformatics analysis of gene panels
At the time of surgery only, when fresh tumor is resected

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between the infiltration of CAF and immunosuppressive immune cells and with clinicopathological parameters and patient prognosis (relapse free-survival, overall survival) in stage III NSCLC exposed to immunotherapy
Time Frame: Between September 2018 and December 2021, receiving concomitant radiochemotherapy followed by durvalumab (maintenance)
Analyze CAF and immunosuppressive immune infiltration in a cohort of unresectable stage III lung carcinoma treated with radiochemotherapy followed by immunotherapy, assessing correlation between immunosuppressive subpopulations and clinical parameters and patient outcome. We will use a multiplexing immunofluorescence assay
Between September 2018 and December 2021, receiving concomitant radiochemotherapy followed by durvalumab (maintenance)
Comparative analysis of the modifications of phenotype and functions of MDSC and T lymphocytes when exposed to CAF extracted from patient tumor tissue
Time Frame: At the time of surgery only, when fresh tumor is resected
Functional in vitro studies of the effect of CAF on phenotype and function of T lymphocytes and of MDSC being extracted from resected NSCLC prospectively collected
At the time of surgery only, when fresh tumor is resected

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Bordeaux

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

December 1, 2025

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

August 28, 2023

First Submitted That Met QC Criteria

August 28, 2023

First Posted (Actual)

September 6, 2023

Study Record Updates

Last Update Posted (Actual)

July 30, 2025

Last Update Submitted That Met QC Criteria

July 29, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHUBX 2023/34

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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