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

Cel

Esophageal carcinoma (EC) is among the top 10 deadliest cancers worldwide. The current standard
therapy 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 and
inform 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 longterm
effects of successful treatments. Tumor neo-antigens, generated by somatically mutated
cancer genes, have been recently implicated in the activation of the most efficient anti-tumor T cell
response capable of controlling tumor progression, induced by immune checkpoint blockade
immunotherapy. This raises the question as to whether clinical responses induced by NACR in a
fraction of ECs may be linked to the stimulation of clinically relevant T cell responses against tumor
neoantigens, implying that activating tumor immunity in the non-responding ones may improve
clinical responses. Objective of this proof-of-concept study is hence to address this question through
the implementation of a high-throughput platform to assess neoantigen-specific T cell responses in
ECs in the course of NACR.