Abstract 3856: Nodal metastasis as an immune indicator in cancer (ca) therapy
Authors: Fugere Bradley , Chen Jim , Fugere Tyler C. , Mazahreh Farah , Thalambadu Nishanth , Safar A Mazin 
Published: March 2024

Introduction: Nodal Metastasis as an Immune Indicator in Cancer (Ca) Therapy Staging (sg) is widely used to identify appropriate treatment options & implement therapy. Tumor-Node-Metastasis (TNM) is the most utilized sg system. In it, nodal involvement is viewed simply as an adverse metric without biologic connotation, and gross metastasis (M1) eclipses other variables and denotes the least favorable sg. Ca’s ability to thrive within the lymph node itself was intriguing to us in the immune-oncology (IO) era. Failure to overcome an immunogenic ca (e.g., dysfunctional apoptosis) leads to T-cell exhaustion (TCE) typified by PD-1 expression. Immune Checkpoint Inhibitors (ICI) address TCE by intercepting the PD-1:PDL-1 synapse. We reasoned that immune actions are distinct in tumor beds vs nodes & hypothesized that immunogenic N(+), implies ca’s ability to defend itself (e.g., PDL-1 expression); N(0), reflects immune susceptibility and effective clearance outside the tumor bed. In the latter scenario, TCE is nonexistent; ICIs are less beneficial. Tumor beds (T, M) are sanctuaries exempt from immune action due to factors such as hypoxia, acidity, and poor tumor vasculature which lead to poor T-cell trafficking, to name a few. M1 develop from circulating ca stem cells, an immune-exempt entity.

Methods: We examined the interaction between ICIs & nodal involvement dichotomizing surveillance, epidemiology and end results SEER cases into N(0) or N(+) within M1 melanoma & lung cancer. 2005, 2015-17 denote pre-, and post ICI, respectively to provide mature survival data.

Results: Table 1 depicts the 4- or 5-year overall survival in the specified subsets.

Conclusions: ICI benefit is more prominent in N(+) ca, where TCE is likely. N(0) ca represents immune-prone ca with less TCE & need to be viewed as a biologically distinct subset. Agents influencing T-cell access (angiogenic)/functionality should be considered in these cases. Finally, we suggest that PDL-1 testing should specify testing sites as nodal vs tumor bed expression.

Expectations SEER results: % Overall Survival at 5-y (melanoma) or 4-y (Lung ca) Pre-ICI Post ICI Metric Melanoma Mechanism 2005 2015 Increment in 5yr OS N(0) favorable prognosis Immunogenic tumor N(0): 302 cases 20 29 8 (20 -12) N+ Predicts benefit to ICI T-cell exhaustion in N(+) only N(+): 210 cases 12 37 N(+): +25 &gt; N(0): +9 2005 2017 Increment in 4yr OS Lung Cancer N(0) similar to N(+) Less immunogenic tumor N(0) 9,583 cases 18 18 4 (18 -14) N+ Predicts benefit to ICI T-cell exhaustion in N(+) only N(+): 17,887 cases 14 20 +6

Citation Format: Bradley Fugere, Jim Chen, Tyler C. Fugere, Farah Mazahreh, Nishanth Thalambadu, A Mazin Safar. Nodal metastasis as an immune indicator in cancer (ca) therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3856.