TY - JOUR
T1 - Mucosal tumor vaccination delivering endogenous tumor antigens protects against pulmonary breast cancer metastases
AU - Oltmanns, Friederike
AU - Antão, Ana Vieira
AU - Irrgang, Pascal
AU - Viherlehto, Vera
AU - Jörg, Leticia
AU - Schmidt, Anna
AU - Wagner, Jannik T.
AU - Rückert, Michael
AU - Flohr, Ann Sophie
AU - Geppert, Carol Imanuel
AU - Frey, Benjamin
AU - Bayer, Wibke
AU - Gravekamp, Claudia
AU - Tenbusch, Matthias
AU - Gaipl, Udo
AU - Lapuente, Dennis
N1 - Publisher Copyright:
© Author(s) (or their employer(s)) 2024.
PY - 2024/3/7
Y1 - 2024/3/7
N2 - 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.
AB - 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.
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U2 - 10.1136/jitc-2023-008652
DO - 10.1136/jitc-2023-008652
M3 - Article
C2 - 38458636
AN - SCOPUS:85187520459
SN - 2051-1426
VL - 12
JO - Journal for ImmunoTherapy of Cancer
JF - Journal for ImmunoTherapy of Cancer
IS - 3
M1 - e008652
ER -