Related Experiment Video
Updated: Nov 25, 2025
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Discordant Responses Between Primary Head and Neck Tumors and Nodal Metastases Treated With Neoadjuvant Nivolumab:
Dante J Merlino1, Jennifer M Johnson2, Madalina Tuluc3
1Department of Otolaryngology - Head and Neck Surgery, Thomas Jefferson University, Philadelphia, PA, United States.
Abstract:
PD-1 blockade represents a promising treatment in patients with head and neck squamous cell carcinoma (HNSCC). We analyzed results of a neoadjuvant randomized window-of-opportunity trial of nivolumab plus/minus tadalafil to investigate whether immunotherapy-mediated treatment effects vary by site of involvement (primary tumor, lymph nodes) and determine how radiographic tumor shrinkage correlates with pathologic treatment effect.
Patients And Methods:
Forty-four patients enrolled in trial NCT03238365 were treated with nivolumab 240 mg intravenously on days 1 and 15 with or without oral tadalafil, as determined by random assignment, followed by surgery on day 31. Radiographic volumetric response (RVR) was defined as percent change in tumor volume from pretreatment to posttreatment CT scan. Responders were defined as those with a 10% reduction in the volume of the primary tumor or lymph nodes (LN). Pathologic treatment effect (PTE) was defined as the area showing fibrosis or lymphohistiocytic inflammation divided by total tumor area.
Results:
Sixteen of 32 patients (50%) with pathologic evidence of LN involvement exhibited discordant PTE between primary sites and LN. In four patients with widely discordant adjacent LN, increased PTE was associated with increased infiltration of tumor CD8+ T cells and CD163+ macrophages, whereas stromal regulatory T cells were associated with low nodal PTE. RVR correlated with PTE at both primary tumor (slope = 0.55, p < 0.001) and in LN (slope = 0.62, p < 0.05). 89% (16/18) of radiographic non-responders with T1-T3 primary sites had no (n = 7) or minimal PTE (n = 9), whereas 15/17 (88%) of radiographic responders had moderate (n = 12) or complete (n = 3) PTE.
Conclusion:
Nivolumab often induces discordant treatment effects between primary tumor sites and metastatic lymph nodes within subjects. This treatment discordance was also demonstrated in adjacent lymph nodes, which may correlate with local immune cell makeup. Finally, although these data were generated by a relatively small population size, our data support the use of early radiographic response to assess immunotherapy treatment effect in HNSCC.
Insights
Immunotherapy with nivolumab can cause different treatment effects in head and neck squamous cell carcinoma (HNSCC) primary tumors versus lymph nodes. Early radiographic response can help assess immunotherapy effectiveness in HNSCC patients.
Area of Science:
- Oncology
- Immunotherapy
- Head and Neck Cancer
Background:
- PD-1 blockade with nivolumab shows promise for head and neck squamous cell carcinoma (HNSCC).
- Investigating treatment effects in primary tumors versus lymph nodes is crucial for optimizing immunotherapy.
Purpose of the Study:
- To analyze immunotherapy-mediated treatment effects in HNSCC based on tumor site (primary vs. lymph nodes).
- To correlate radiographic tumor shrinkage with pathologic treatment effect in HNSCC patients receiving nivolumab.
Main Methods:
- A neoadjuvant randomized window-of-opportunity trial (NCT03238365) involving 44 HNSCC patients treated with nivolumab +/- tadalafil.
- Radiographic volumetric response (RVR) assessed tumor volume changes; pathologic treatment effect (PTE) evaluated fibrosis and inflammation.
- Tumor-infiltrating immune cells (CD8+, CD163+, regulatory T cells) analyzed in relation to PTE.
Main Results:
- Fifty percent of patients with lymph node (LN) involvement showed discordant PTE between primary sites and LNs.
- Radiographic volumetric response (RVR) correlated significantly with PTE in both primary tumors (p < 0.001) and LNs (p < 0.05).
- Radiographic responders demonstrated moderate to complete PTE, while non-responders had minimal or no PTE.
Conclusions:
- Nivolumab can induce differing treatment effects between primary HNSCC tumors and metastatic lymph nodes.
- Discordant treatment effects in lymph nodes may be linked to local immune cell composition.
- Early radiographic response is a valuable tool for assessing immunotherapy treatment effect in HNSCC.
