Here, we describe a combination strategy of black phosphorus (BP)-based photothermal therapy together with anti-CD47 antibody (aCD47)-based immunotherapy to synergistically enhance cancer treatment. Tumour resistance to immune checkpoint blockades in most cancers due to immune escape from host surveillance, along with the initiation of metastasis through immunosuppressive cells in the tumour microenvironment, remains a significant challenge for cancer immunotherapy. aCD47, an agent for CD47/SIRPα axis blockade, induces modest phagocytic activity and a low response rate for monotherapy, resulting in failures in clinical trials. We showed that BP-mediated ablation of tumours through photothermal effects could serve as an effective strategy for specific immunological stimulation, improving the inherently poor immunogenicity of tumours, which is particularly useful for enhancing cancer immunotherapy. BP in combination with aCD47 blockade activates both innate and adaptive immunities and promotes local and systemic anticancer immune responses, thus offering a synergistically enhanced effect in suppression of tumour progression and in inducing abscopal effects for inhibition of metastatic cancers. Our combination strategy provides a promising platform in which photothermal agents could help to enhance the therapeutic efficacy of immunotherapy.

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Summary Allopolyploidization, which entails interspecific hybridization and whole genome duplication (WGD), is associated with emergent genetic and epigenetic instabilities that are thought to contribute to adaptation and evolution. One frequent genomic consequence of nascent allopolyploidization is homoeologous exchange (HE), which arises from compromised meiotic fidelity and generates genetically and phenotypically variable progenies. Here, we used a genetically tractable synthetic rice segmental allotetraploid system to interrogate genome‐wide DNA methylation and gene expression responses and outcomes to the separate and combined effects of hybridization, WGD and HEs. Progenies of the tetraploid rice were genomically diverse due to genome‐wide HEs that affected all chromosomes, yet they exhibited overall methylome stability. Nonetheless, regional variation of cytosine methylation states was widespread in the tetraploids. Transcriptome profiling revealed genome‐wide alteration of gene expression, which at least in part associates with changes in DNA methylation. Intriguingly, changes of DNA methylation and gene expression could be decoupled from hybridity and sustained and amplified by HEs. Our results suggest that HEs, a prominent genetic consequence of nascent allopolyploidy, can exacerbate, diversify and perpetuate the effects of allopolyploidization on epigenetic and gene expression variation, and hence may contribute to allopolyploid evolution.

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