Mucosal tumor vaccination delivering endogenous tumor antigens protects against pulmonary breast cancer metastases
Friederike Oltmanns, Ana Vieira Antão, Pascal Irrgang, Vera Viherlehto, Leticia Jörg, Anna Schmidt, Jannik T. Wagner, Michael Rückert, Ann-Sophie Flohr, Carol I. Geppert, Benjamin Frey, Wibke Bayer, Claudia Gravekamp, Matthias Tenbusch, Udo S. Gaipl, Dennis Lapuente
Abstract
BACKGROUND: Generally, early-stage breast cancer has a good prognosis. However, if it spreads systemically, especially with pulmonary involvement, prospects worsen dramatically. Importantly, tumor-infiltrating T cells contribute to tumor control, particularly intratumoral T cells with a tissue-resident memory phenotype are associated with an improved clinical outcome. METHODS: Here, we use an adenoviral vector vaccine encoding endogenous tumor-associated antigens adjuvanted with interleukin-1β to induce tumor-specific tissue-resident memory T cells (TRM) in the lung for the prevention and treatment of pulmonary metastases in the murine 4T1 breast cancer model. RESULTS: The mucosal delivery of the vaccine was highly efficient in establishing tumor-specific TRM in the lung. Concomitantly, a single mucosal vaccination reduced the growth of pulmonary metastases and improved the survival in a prophylactic treatment. Vaccine-induced TRM contributed to these protective effects. In a therapeutic setting, the vaccination induced a pronounced T cell infiltration into metastases but resulted in only a minor restriction of the disease progression. However, in combination with stereotactic radiotherapy, the vaccine increased the survival time and rate of tumor-bearing mice. CONCLUSION: In summary, our study demonstrates that mucosal vaccination is a promising strategy to harness the power of antitumor TRM and its potential combination with state-of-the-art treatments.