2024 World Conference on Lung Cancer (WCLC) - Posters-P3.08E.01 Perioperative Chemoimmunotherapy Rescue Cold HLA-Deficient Tumors Inducing Strong Immune Responses and Long-Term Survival

P3.08E.01 Perioperative Chemoimmunotherapy Rescue Cold HLA-Deficient Tumors Inducing Strong Immune Responses and Long-Term Survival

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The study conducted by Marta Molina-Alejandre and colleagues focuses on perioperative chemoimmunotherapy (ChIO) and its effects on cold HLA-deficient tumors, particularly in the context of non-small cell lung cancer (NSCLC). The research aims to assess the HLA status and tumor microenvironment (TME) to understand the mechanisms of response and resistance to ChIO.<br /><br />HLA (Human Leukocyte Antigen) status is crucial because a loss of heterozygosity (LOH) in HLA reduces the repertoire of neoantigens that tumor cells can present, thereby impacting the immune response. The study identifies that HLA class I deficient tumors significantly influence the TME, although this is not directly associated with clinical outcomes. Despite that, ChIO can induce a strong immune response involving Tertiary Lymphoid Structures (TLS) and T cells in these HLA-deficient tumors. This immune response can lead to complete pathological responses (CPRs) and long-term survival for patients.<br /><br />The results reveal that while HLA-deficient tumors pose a challenge due to their reduced neoantigen presentation, they are not entirely resistant to therapy. The induction of significant immune responses through ChIO in these tumors emphasizes the potential for personalized cancer treatments targeting the TME.<br /><br />The study was funded by various institutions, including Bristol-Myers Squibb and the Spanish Ministry of Science and Innovation. This comprehensive research highlights the potential for ChIO as an effective therapeutic strategy, emphasizing the importance of understanding tumor immunogenicity and the role of TME in cancer treatment. The insights gained could be pivotal in designing new treatment protocols for NSCLC and other cancers with similar HLA deficiencies.

Asset Subtitle

Marta Molina-Alejandre

Meta Tag

Speaker Marta Molina-Alejandre

Topic Local-Regional NSCLC

Keywords

perioperative chemoimmunotherapy

HLA-deficient tumors

non-small cell lung cancer

tumor microenvironment

immune response

tertiary lymphoid structures

personalized cancer treatments

tumor immunogenicity

complete pathological responses

HLA class I deficiency