Tumor surgery can create an inflammatory
trauma to aggravate residual
tumor “seed” to colonize pre-metastatic niches (PMNs)
“soil” at secondary sites, thereby promoting post-operative
metastasis. However, two-pronged strategies for post-surgical elimination
of asynchronous “seeds” and “soil” at
different regions are currently lacking. Here, we have designed a
hydrogel that can be injected into a resection cavity, where it immediately
forms a scaffold and gradually degrades responding to enriched reactive
oxygen species at adjacent trauma for local delivery and on-demand
release of autologous cancer cells succumbing to oncolysis (ACCO)
and anti-inflammatory agent. The autologous cell source self-provides
a whole array of tumor-associated antigens, and the oncolysis orchestration
of a subcellular cascade confers a self-adjuvanting property, together
guaranteeing high immunogenicity of the ACCO vaccine that enables
specific antitumor immunization. In parallel, inflammation alleviation
exerted bidirectional functions to reshape the local immune landscape
and resuscitate ACCO, leading to the eradication of residual tumor
“seeds” while simultaneously intercepting the “seed–soil”
crosstalk to normalize distant lung leading to regression of pre-existing
PMN “soil”. As a result, regional and metastatic recurrence
were completely thwarted. Together, this framework synchronizing oncolysis
immunization and inflammation alleviation provides an effective option
for post-operative suppression of metastasis.