# Dissecting the role of B lineage cells in mediating response of resectable lung cancer to neoadjuvant immune-based therapy > **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2024 · $670,358 ## Abstract PROJECT SUMMARY Neoadjuvant and perioperative chemoimmunotherapy are the standard of care for the treatment of patients with resectable non-small cell lung cancer (NSCLC). Unfortunately, the majority of patients with resectable NSCLC do not benefit from neoadjuvant/perioperative immune checkpoint inhibitor (ICI)-based therapies for reasons that are unclear. Efforts to develop more effective treatment strategies that bypass therapeutic resistance have been hampered by our limited understanding of the mechanisms that govern response to ICIs and that thus could serve as validated biomarkers to guide neoadjuvant/perioperative ICI treatment. Our long-term objectives are to develop rational neoadjuvant/perioperative combination therapies that prevent resistance and increase benefit from ICI-based treatments. Recently, we analyzed NSCLCs from patients treated with chemotherapy (CT) plus dual ICIs in the phase 2 NEOSTAR trial (PI: Cascone) and found those from responders contained enhanced B cell fractions and markers of tertiary lymphoid structures (TLS) compared to nonresponders. These findings were recapitulated when using neoadjuvant combinations of ICI plus novel immunomodulatory agents in our recently reported phase 2 trial, NeoCOAST. To build on these observations from our clinical trials, we performed preliminary spatial-omics analysis of a pilot cohort of NSCLCs from patients treated with neoadjuvant CT+ICI and with varying response to therapy. We found that pathologic response was associated with aggregation of B cells into organized structures (e.g., TLS) with elevated expression of anti-tumor B cell signatures and enhanced cell-cell communication with the tumor immune microenvironment. Preclinically, we found that neoadjuvant ICI-based therapy was the most effective treatment at reducing frequency of metastases and prolonging survival in our human-relevant models of spontaneously metastatic NSCLC and therapeutic efficacy was once again tightly coupled with enhanced B cell infiltration. Consequently, we hypothesize that B cell transcriptional, immunogenomic, and spatial landscapes in neoadjuvant CT+ICI-treated NSCLC patients differ by MPR, and that B cell-mediated cytotoxic antitumor responses, including their interaction with T cells, augment the efficacy of neoadjuvant ICI-based therapy in early-stage NSCLC. We will test our hypothesis by determining the transcriptional, immunogenomic, and spatial landscapes of B lineage cells in human NSCLC treated with neoadjuvant ICI-based therapy (Aim 1); interrogating the impact of B cells on T cell-mediated responses to neoadjuvant ICI-based therapy in murine models of NSCLC (Aim 2); and investigating the utility of B cell-centric phenotypes in predicting benefit of neoadjuvant ICI-based therapy in resectable NSCLC from unique clinical trials (Aim 3). This proposal will leverage a platform of unique, global clinical trial cohorts of NSCLC, novel human-relevant mouse models of NSCLC, as well as state-of... ## Key facts - **NIH application ID:** 10998089 - **Project number:** 1R01CA287734-01A1 - **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR - **Principal Investigator:** Tina Cascone - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $670,358 - **Award type:** 1 - **Project period:** 2024-08-01 → 2029-07-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10998089 ## Citation > US National Institutes of Health, RePORTER application 10998089, Dissecting the role of B lineage cells in mediating response of resectable lung cancer to neoadjuvant immune-based therapy (1R01CA287734-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10998089. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*