2024 Asia Conference on Lung Cancer (ACLC) - Poster & ePosters-PP01.79

PP01.79 - Linglu Yi

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The study investigates the effect of low-dose radiotherapy (LDRT) on the immune response in small cell lung cancer (SCLC) by examining the role of CD9 immune-related extracellular vesicles (EVs). Researchers from Sichuan University's West China Hospital have found that combining LDRT with immune checkpoint inhibitors (ICIs) enhances CD8 T cell and dendritic cell (DC) infiltration in SCLC. The study particularly focuses on how CD9 EVs contribute to antigen delivery, promoting DC maturation and T cell activation.<br /><br />The researchers used a SCLC patient-derived organoid/xenograft (PDO/PDX) model to study the antigen delivery mechanism. LDRT-treated extracellular vesicles (EVs) from SCLC showed increased internalization by DCs, correlating with higher expression of maturation markers such as CD86 on DCs and activation markers like CD69 on T cells. The duration of contact between DCs and T cells presenting antigens was prolonged, enhancing the immune response. The study highlights that EV subtype influences antigen delivery capabilities, and LDRT-modified EVs exhibit superior antigen delivery than controls.<br /><br />The research implies that LDRT-treated CD9 EVs facilitate the transfer of a broader repertoire of antigens, potentially leading to robust tumor-specific T cell responses. By using immunopeptide-TCR analysis, the researchers identified different antigenic peptides associated with effective immune activation, particularly those targeting genes MIF and STMN1 that are prominent in SCLC.<br /><br />This study underscores the potential of LDRT in enhancing the efficacy of immunotherapy through improved antigen presentation and T cell activation in SCLC, offering a promising approach to cancer treatment. The findings suggest that the strategic incorporation of LDRT with immune modulators might significantly improve therapeutic outcomes by leveraging EV-mediated immune activation.

Keywords

low-dose radiotherapy

immune response

small cell lung cancer

CD9 extracellular vesicles

immune checkpoint inhibitors

dendritic cell maturation

antigen delivery

T cell activation

tumor-specific response

Sichuan University