2026 Proffered Presentations
S160: CHEMO-IMMUNOMODULATION AS A MECHANISTIC RATIONALE FOR COMBINED IMMUNO-ONCOLOGY THERAPY IN SINONASAL SCC
Yen Vu; Hinduja Sathishkumar; Jindal Sonali; Padmanee Sharma; Ehab Hanna; Robert Saddawi-Konefka; Moran Amit; MD Anderson Cancer Center
Background: Sinonasal squamous cell carcinoma (SNSCC) represents a rare malignancy with poor outcomes despite multimodal therapy. Chemo-immunomodulation—the concept that chemotherapy exerts immunomodulatory effects beyond direct cytotoxicity—fundamentally alters host antitumor immunity through enhanced immune cell infiltration and reduced immunosuppression. Our preclinical studies demonstrated that low-dose chemotherapy sequenced with checkpoint blockade potentiated anti-tumor responses by reversing myeloid-derived suppressor cell-mediated immunosuppression. However, the extent and characteristics of chemo-immunomodulation in human SNSCC remain poorly characterized. We hypothesize that chemotherapy induces immunogenic tumor microenvironment remodeling in SNSCC, creating conditions favorable for enhanced immunotherapy efficacy.
Methods: SNSCC tissue specimens from MD Anderson patients were analyzed using multiplex COMET imaging (Lunaphore Technologies) to simultaneously visualize immune cell markers and tissue architecture. We compared samples from three cohorts: patients who received surgery alone, patients who received chemotherapy alone (platinum or taxane-based), and patients who received both chemotherapy and immunotherapy (pembrolizumab). COMET images were analyzed to assess immune cell abundance and spatial organization, correlating tumor microenvironment features, including immune infiltration patterns, inflammatory cell presence, and tertiary lymphoid structure (TLS) composition—with clinical response and outcomes.
Results: Multiplex imaging revealed substantial inflammatory infiltrates and enhanced immune cell recruitment in peritumoral regions of chemotherapy-treated SNSCC specimens compared to untreated controls. Analysis showed increased CD4+ and CD8+ T cells, B cells, and diverse inflammatory cell populations in chemotherapy-treated samples. These infiltrates exhibited organized spatial distribution with distinct clustering of immune cell subsets and formation of tertiary lymphoid structures with organized B-cell follicles and T-cell zones (Figure 1). Clinical correlation revealed distinct outcome patterns, patients who received surgery alone experienced disease recurrence within the follow-up period; in contrast, patients treated with chemotherapy alone demonstrated stable disease or partial responses (Figure 2), with sustained disease control maintained throughout the observation period. The patient receiving combination chemotherapy and immunotherapy (Figure 3) achieved partial response with measurable tumor reduction and continued response at last follow-up. Disease-free survival was longest in patients receiving chemotherapy-based treatments, with the combination therapy patient showing the most durable response. These clinical outcomes correlated directly with the degree of immune cell infiltration and tertiary lymphoid structure formation observed on multiplex imaging, suggesting that treatment-induced immunological remodeling (Figure 3) translates to therapeutic benefit.
Conclusions: These findings provide evidence of chemo-immunomodulation in SNSCC, manifested by chemotherapy-associated immune cell infiltration and tertiary lymphoid structure formation. These immunological changes indicate that chemotherapy can reshape the tumor microenvironment in ways that enhance immunotherapy efficacy, providing mechanistic rationale for combined approaches in SNSCC and identifying potential predictive biomarkers for response. The correlation between immune microenvironment remodeling and clinical outcomes supports the therapeutic potential of rationally sequenced chemo-immunotherapy in this challenging malignancy.
