Menu
MapConnectionsTopicsBulgariaThe Night (K-TRIO)Marie Skłodowska-CurieFor studentsFor teachersMethodologySurprise me
H2020Individual fellowship2018–2020

IC_IL_EC_2017 · Investigating the effects of immunogenic chemoradiation in shaping the immune landscape of esophageal cancers

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2018-03-01 → 2020-05-19
EU contribution
€168,277
Participants
1
Scheme
MSCA-IF-EF-SE

Lines connect the coordinator with its partners.

Results in brief

Investigating the effects of immunogenic chemoradiation in shaping the immune landscape ofesophageal cancers

"Esophageal cancer is among the top 10 deadliest cancers worldwide, with the adenocarcinoma (EAC) variant representing the predominant histological subtype in western countries. The standard therapy for esophageal adenocarcinoma is pre-operative neoadjuvant chemo-radiation and surgery. Only about 20% of patients achieve a pathological complete response (pCR) and increased 5-year survival after NACR. Understanding the mechanisms of response to NACR is pivotal to better stratify patients and inform the design of more efficacious therapies. Evidence suggests that the neoadjuvant chemo-radiatiotherapy stimulates anti-cancer immune responses, which may contribute to the long-term effects of successful treatments. Tumor-specific responses of T lymphocytes, cells of the immune system, are directed against proteins from DNA mutations in the tumor, that are recognized as ""non-self"". This project investigates whether the apathologic complete response to neoadjuvant chemo-radiotherapy treatment achieved in a fraction of patients with esophageal cancer may result from the stimulation of tumor-specific immune responses that contributes to cancer cell elimination. This proof-of concept study may lead to the definition of novel and more efficacious immunotherapeutic approaches for EAC, including the design of cancer vaccines to newly diagnosed cases to block disease progression, with a strong impact in ameliorating the patients quality of life. The overall objective of this project are to investigate the molecular and cellular mechanisms of immune response against esophageal cancer upon neoadjuvant chemo-radiotherapy, by comparing responder and non-responder patients for the molecular pathways in the tumor, the infiltration of cells of the immune system in the tumor and the regognition of tumor DNA mutation by the patients immune system."

Data: CORDIS, © European Union

Project objective

Esophageal carcinoma (EC) is among the top 10 deadliest cancers worldwide. The current standardtherapy for ES is neoadjuvant (pre-operative) chemoradiation (NACR) followed by surgery. However,only 30% of patients achieve a complete pathological response (CPR) and long-term survival.Understanding the mechanisms of response to NACR is hence pivotal to better stratify patients andinform the design of more efficacious therapies. Evidence from some tumors suggests that NACR is“immunogenic” and stimulates anti-cancer immune responses, which may contribute to the longtermeffects of successful treatments. Tumor neo-antigens, generated by somatically mutatedcancer genes, have been recently implicated in the activation of the most efficient anti-tumor T cellresponse capable of controlling tumor progression, induced by immune checkpoint blockadeimmunotherapy. This raises the question as to whether clinical responses induced by NACR in afraction of ECs may be linked to the stimulation of clinically relevant T cell responses against tumorneoantigens, implying that activating tumor immunity in the non-responding ones may improveclinical responses. Objective of this proof-of-concept study is hence to address this question throughthe implementation of a high-throughput platform to assess neoantigen-specific T cell responses inECs in the course of NACR.

Original text from CORDIS.

Participants

  • OSPEDALE SAN RAFFAELE SRL · MilanoCoordinatorItaly

Links

Data: CORDIS, © European Union