Neoadjuvant Immunotherapy, Chemoradiotherapy in Patients With T2-4NO-1 NSCLC

Tumor-draining lymph nodes (TDLN) play a key role in the immune response against tumors and are often part of the healthy tissue that surrounds tissue exposed to radiotherapy. Results of a study investigating the immune-modulating effects of neoadjuvant immunotherapy and CRT on TDLN in patients with T2-4NO-1 NSCLC were presented at the ESMO Congress 2023.

The researchers collected resected TDLN from participants in the INCREASE trial (which investigated the addition of neoadjuvant immunotherapy to CRT prior to surgical resection in patients with locally advanced NSCLC) who received neoadjuvant ipilimumab/nivolumab combined with CRT (n=25) and a control cohort of matched NSCLC patients treated with standard CRT induction therapy (n=25). TDLN were selected based on low, intermediate, or high dose of radiation received and stained with duplex immunohistochemistry for CD8/Ki67, PD1/FOXP3, and CD8/cleaved caspase-3.

Results showed that higher counts of proliferating CD8 T cells were observed within TDLN in all three categories of radiation exposure in the INCREASE cohort compared with control patients (P<.0001, P=.02, and P<.0001 for low, intermediate, and high dose, respectively), as well as higher counts of PD1+ Tregs (P<.0001 for all nodes). Additionally, the researchers observed higher numbers of Ki67+ CD8 T cells and PD1+ Tregs with increasing radiation dose (INCREASE high vs low dose, P=.0095 for CD8 T cells and P=.0298 for Tregs). The researchers did not observe a relationship between radiation dose exposure and the induction of apoptosis by cleaved caspase-3 in CD8 T cells.

The study authors concluded that higher rates of proliferating CD8 T cells and activated PD1+ Tregs in TDLN were seen when immunotherapy was added to induction CRT in patients with T2-4NO-1 NSCLC, “suggesting the enhanced priming of effector CD8 T cells, accompanied by a simultaneous increase in Tregs. High radiation dose led to an increase of CD8 T cells and Tregs in the INCREASE cohort. Further analyses with spatial transcriptomics and quantitative pathology imaging is needed to reveal spatial positioning of PD1+ Tregs in relation to proliferating CD8 T cells.”

Source: Ulas EB, Vrijmoet A, Koomen S, et al. Immune-modulating effects on tumor draining lymph nodes following neoadjuvant chemoradiotherapy combined with immunotherapy in patients with T2-4NO-1 NSCLC. Abstract of a poster presented at the ESMO Congress 2023; October 20-24, 2023; Madrid, Spain.