Photothermal Prussian blue nanoparticles generate potent multi-targeted tumor-specific T cells as an adoptive cell therapy.

Prussian blue nanoparticle-based photothermal therapy (PBNP-PTT) is an effective tumor treatment capable of eliciting an antitumor immune response. Motivated by the ability of PBNP-PTT to potentiate endogenous immune responses, we recently demonstrated that PBNP-PTT could be used ex vivo to generate tumor-specific T cells against glioblastoma (GBM) cell lines as an adoptive T cell therapy (ATCT). In this study, we further developed this promising T cell development platform. First, we assessed the phenotype and function of T cells generated using PBNP-PTT. We observed that PBNP-PTT facilitated CD8+ T cell expansion from healthy donor PBMCs that secreted IFNγ and TNFα and upregulated CD107a in response to engagement with target U87 cells, suggesting specific antitumor T cell activation and degranulation. Further, CD8+ effector and effector memory T cell populations significantly expanded after co-culture with U87 cells, consistent with tumor-specific effector responses. In orthotopically implanted U87 GBM tumors in vivo, PBNP-PTT-derived T cells effectively reduced U87 tumor growth and generated long-term survival in >80% of tumor-bearing mice by Day 100, compared to 0% of mice treated with PBS, non-specific T cells, or T cells expanded from lysed U87 cells, demonstrating an enhanced antitumor efficacy of this ATCT platform. Finally, we tested the generalizability of our approach by generating T cells targeting medulloblastoma (D556), breast cancer (MDA-MB-231), neuroblastoma (SH-SY5Y), and acute monocytic leukemia (THP-1) cell lines. The resulting T cells secreted IFNγ and exerted increased tumor-specific cytolytic function relative to controls, demonstrating the versatility of PBNP-PTT in generating tumor-specific T cells for ATCT.

A female's past experience with predators affects male courtship and the care her offspring will receive from their father.

Differential allocation occurs when individuals adjust their reproductive investment based on their partner's traits. However, it remains unknown whether animals differentially allocate based on their partner's past experiences with predation risk. If animals can detect a potential mate's experience with predators, this might inform them about the stress level of their potential mate, the likelihood of parental effects in offspring and/or the dangers present in the environment. Using threespined stickleback (Gasterosteus aculeatus), we examined whether a female's previous experience with being chased by a model predator while yolking eggs affects male mating effort and offspring care. Males displayed fewer conspicuous courtship behaviours towards females that had experienced predation risk in the past compared with unexposed females. This differential allocation extended to how males cared for the resulting offspring of these matings: fathers provided less parental care to offspring of females that had experienced predation risk in the past. Our results show for the first time, to our knowledge, that variation among females in their predator encounters can contribute to behavioural variation among males in courtship and parental care, even when males themselves do not encounter a predator. These results, together with previous findings, suggest that maternal predator exposure can influence offspring development both directly and indirectly, through how it affects father care.

Effect of maternal predator exposure on the ability of stickleback offspring to generalize a learned colour-reward association.

Maternal stress can have long-term negative consequences for offspring learning performance. However, it is unknown whether these maternal effects extend to the ability of offspring to apply previously learned information to new situations. In this study, we first demonstrate that juvenile threespine sticklebacks, Gasterosteus aculeatus, are indeed capable of generalizing an association between a colour and a food reward learned in one foraging context to a new foraging context (i.e. they can apply previously learned knowledge to a new situation). Next, we examined whether this ability to generalize was affected by maternal predator stress. We manipulated whether mothers were repeatedly chased by a model predator while yolking eggs (i.e. before spawning) and then assessed the learning performance of their juvenile offspring in groups and pairs using a colour discrimination task that associated a colour with a food reward. We found that maternal predator exposure affected the tendency of offspring to use social cues: offspring of predator-exposed mothers were faster at copying a leader's behaviour towards the rewarded colour than offspring of unexposed mothers. However, once the colour-reward association had been learned, offspring of predator-exposed and unexposed mothers were equally able to generalize their learned association to a new foraging task. These results suggest that offspring of predator-exposed mothers might be able to overcome learning deficits caused by maternal stress by relying more on social cues.