A study presented at the annual European Society of Medical Oncology Congress 2025 and published in the journal Annals of Oncology reveals a promising association between SARS-COV-2 vaccination and outcomes for cancer patients receiving immune checkpoint inhibitors (ICIs).
The researchers based their current study on their previous pre-clinical work demonstrating that mRNA vaccination induced anti-tumor immunity by increasing the expression of programmed death-ligand 1 (PD-L1) on tumor cells. PD-L1, a checkpoint ligand, interacts with a checkpoint protein called programmed death one (PD-1). The binding of PD-1, found on the surface of immune cells, to PD-L1 stops the immune response. Thus, some very promising anti-cancer immunotherapy approaches involve disrupting the connection between PD-1 and PD-L1, thereby taking the brakes off the immune system.
The updates to this research show the next step by showing that the pre-clinical findings also apply in the clinical setting. The researchers looked for patients with Stage III/IV non-small cell lung cancer (NSCLC) or metastatic melanoma who had undergone biopsies during their treatment. Through database searches, the researchers identified 2,406 NSCLC and 757 melanoma patients. In addition, the study included data from 5,524 patients whose medical records didn’t clearly define the type of cancer diagnosis, but pathology reports included PD-L1 readouts. The researchers referred to this cohort as “tissue agnostic” as it could represent a variety of different cancer types.
The researchers extracted information about the characteristics of each patient and their cancer, as well as the dates of SARS-COV-2 vaccination, where applicable. The analysis found that NSCLC patients who had received SARS-COV-2 vaccination within 100 days of biopsy exhibited a 23% increase in the PD-L1 mean tumor proportion score (TPS), a percentage of tumor cells that express PD-L1. In addition, those NSCLC patients receiving vaccination within 100 days of biopsy had a 28% increase in the frequency of TPS over 50%.
In the tissue-agnostic cohort, the researchers found a 55% increase in mean TPS when patients received a SARS-COV-2 mRNA vaccination within 100 days.
In addition to validating previous findings on the upregulation of PD-L1 in clinical samples, the researchers also reported that SARS-COV-2 mRNA vaccination improved outcomes for patients receiving ICI.
NSCLC patients treated with ICI and receiving a SARS-COV-2 mRNA vaccination within 100 days had a notable doubling of overall survival (OS). These patients also exhibited a significant improvement in three-year OS. The OS of NSCLC patients not treated with ICI was not impacted by SARS-COV-2 mRNA vaccination.
For the melanoma cohort, receiving a SARS-COV-2 mRNA vaccine within 100 days of ICI significantly extended OS, reduced distant-metastasis-free survival (the time from the start of treatment to the first sign of distant metastasis), and progression-free survival.
The research reported at the recent ESMO meeting shows that SARS-COV-2 mRNA vaccination increases PD-L1 expression in patients with multiple malignancies. Further, vaccination notably improved survival outcomes for patients with NSCLC and melanoma, two cancers commonly treated with ICIs.
Sources: Annal Oncol, Can Immunol Res
