2024 World Conference on Lung Cancer (WCLC) - Posters-P4.07E.07 Spatial Memory B Cells Activation by CXCL13+ Th Cells via the MIF(CD74-CXCR4) Axis may Improve Immunotherapy Efficacy in HER2 Mutant NSCLC

P4.07E.07 Spatial Memory B Cells Activation by CXCL13+ Th Cells via the MIF(CD74-CXCR4) Axis may Improve Immunotherapy Efficacy in HER2 Mutant NSCLC

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This study investigates the potential of immunotherapy and trastuzumab deruxtecan (T-Dxd) for treating HER2 mutant non-small cell lung cancer (NSCLC), focusing on spatial memory B cells activation by CD4CXCL13 T cells through the MIF (CD74-CXCR4) axis. The research, conducted by the Guangdong Lung Cancer Institute, explores whether activating these B cells could enhance immune responses to improve treatment outcomes.<br /><br />The study analyzed 16 patients with HER2 variations, assessing treatment efficacy through objective response rate (ORR), major pathologic response (MPR), and complete pathologic response (PCR). In the immunotherapy group, 42.9% of patients showed partial response, and 57.1% achieved stable disease. For those treated with T-Dxd, 50% had partial responses. The MPR percentages were 50% for immunotherapy and 0% for T-Dxd, while PCRs were 28.6% and 0%, respectively. Adverse effects were observed in the majority, with 28.6% experiencing grade 3 effects.<br /><br />Spatial transcriptomics and single-cell RNA sequencing disclosed a mutually exclusive distribution of CD27 memory B cells and tumor cells. Moreover, the study identified CD4CXCL13 T cells' role in activating these B cells via MIF (CD74-CXCR4) crosstalk, enhancing IgG and IgA production and possibly boosting adaptive immunity against tumors. Immunohistochemistry confirmed such cellular interactions exist.<br /><br />Additional findings showed that T-Dxd treatment led to a complex tumor microenvironment, with both immune effector and suppressor cells present, alongside the upregulation of immune checkpoints. The research highlights the potential of utilizing these neoadjuvant therapies for HER2-mutant NSCLC and offers insights into the intricate tumor microenvironment resulting from T-Dxd treatment.

Asset Subtitle

Huizhao Hong

Meta Tag

Speaker Huizhao Hong

Topic Early-Stage NSCLC

Keywords

immunotherapy

trastuzumab deruxtecan

HER2 mutant

non-small cell lung cancer

spatial memory B cells

CD4CXCL13 T cells

MIF CD74-CXCR4 axis

adaptive immunity

tumor microenvironment

neoadjuvant therapies