Deciphering the role of HLA-E molecules in colorectal cancer immunotherapy HIT Cancer (HLA-E, ImmunoTherapy, Cancer)

• Applicant: Professorin Dr. Barbara Seliger
• Subject Area: Immunology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 546799302

Colorectal cancer (CRC) is worldwide one of the most common cancers and despite recent therapeutic success, only a limited number of CRC patients have a long-term clinical response. In order to improve the therapy for CRC patients, a better understanding of the molecular and cellular immune escape mechanisms, such as alterations in the expression of classical and non-classical HLA class I antigens and in the composition of the tumor microenvironment (TME) is required. Recently, there exists increasing evidence that the non-classical HLA-E antigen has not only an inhibitory, but also a stimulatory activity on anti-tumor immune responses by shaping the TME and interacting with diverse immune cells. To determine the role of HLA-E in CRC, this proposal will (i) decipher the expression and function of HLA-E in tumor lesions, (ii) determine the composition of the TME in association to HLA-E expression, (iii) unravel the underlying molecular mechanisms of immune evasion of disease progression by with focus on microRNA alterations and (iv) investigate their clinical impact based on CRC cohorts using state of the art technologies. An increased knowledge of HLA-E biology in the context of anti-tumoral immune responses will represent the rational for the development of novel immunotherapeutic approaches of CRC patients.

• DFG Programme: Research Grants