Abstract 1597: Immune suppression of the lymph node microenvironment causes oligoprogression of metastatic cancer after neoadjuvant immuno-chemotherapy

Abstract Oligometastatic disease is recognized as an intermediate state between localised and systemically metastasised disease. The diagnosis, treatment and prognosis of oligometastatic disease is currently based mainly on imaging examination. Previous clinical studies indicated that standard systemic therapy followed by radical local therapy was beneficial for survival in tumor patients with oligometastatic disease. However, different clinical outcomes (such as oligopersistant and oligoprogression) were found in synchronous and/or metachronous oligometastatic disease after the same systemic therapy. This report explored potential factors of different outcomes in tumor patients with oligometastatic disease after neoadjuvant immuno-chemotherapy. A lymphoepithelioma-like carcinoma (LELC) case with stage IIIa was synchronous oligometastatic disease, which was treated with neoadjuvant immuno-chemotherapy (four courses of Albumin-Bound Paclitaxel (300 mg), Carboplatin (400 mg) and Durvalumab (500 mg)) and subsequent surgery. Lymph nodes 1R and 4R were considered as oligoprogression and oligopersistant, respectively. Whole exome sequencing results showed that single nucleotide variation (SNV), copy number variation (CNV), tumor mutational burden (TMB), microsatellite instability (MSI), human resource development (HRD) and mutant-allele tumor heterogeneity (MATH) were similar between 1R and 4R samples. Tumor-infiltrating immune cells using a multiplex immunoflourescence histochemistry (mIHC) test revealed that immune checkpoints PD1, PD-L1 and CD39 were high expression and there was a low level of CD8+ T cell in the 4R sample. But levels of CD39+CD8+ and PD-L1+CD8+ T cells were higher in the 1R sample than the 4R sample, suggesting a suppressive tumor immune microenvironment in the 1R oligoprogression lymph node. To demonstrate the result, oligometastatic samples from eight non-small-cell lung cancer (NSCLC) cases with neoadjuvant immuno-chemotherapy and surgery were examined using the mIHC. The results indicated that CD39+CD3+/PD-L1+CD3+/TIM3+CD3+ T cells and/or CD39+CD68+ macrophages in the oligometastatic samples with oligoprogression were high levels. Thus, suppression of tumor-infiltrating immune cells might result in one major factor of different outcomes in oligometastatic disease after neoadjuvant immuno-chemotherapy. Funding Sources: This work was supported by the Wu Jieping Medical Foundation (320.6750.2024-16-16). Citation Format: Peikun Ding, Xiaoxiang Huang, Quanzhou Peng, Kangqi Ren, Longlong Gong, Bin Wang, Lin Yang. Immune suppression of the lymph node microenvironment causes oligoprogression of metastatic cancer after neoadjuvant immuno-chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1597.