SERPINB9 (Serpin Family B Member 9)

Further experiments confirmed that CIITA knockdown decreased BMDM surface MHC-II expression, whereas CIITA overexpression rescued MHC-II expression in SerpinB9-knockout BMDMs and restored their capacity to induce Th1 cell differentiation. In conclusion, this study demonstrates that under WGP induction, SerpinB9 regulates macrophage MHC-II expression and Th1 differentiation-inducing ability by maintaining CIITA expression, providing new insights into macrophage immune regulation mechanisms.

Concurrently, the proportion of DC maturation, macrophage polarization, and CTL infiltration was significantly increased, highlighting CPM's ability to elicit robust antitumor immune responses. This study underscores the potential of CPM as a multifunctional therapeutic agent that simultaneously integrates Sb9 inhibition, ferroptosis induction, and immunotherapy, offering a promising strategy for cancer treatment.

GEM conjugation introduces an additional mechanism of carrier/siRNA interaction in addition to charge-mediated interaction and enables efficient i.v. delivery at lower N/P ratios. Here, we show that co-delivery of GEM and siSPB9 significantly improves antitumor efficacy and remodels the tumor immune microenvironment in pancreatic cancer models, supporting a promising therapeutic strategy.

Our research indicates that SERPINB9 plays a key role in driving tumor progression by enhancing tumor stemness and suppressing TLS. This study stands as the first to elucidate the molecular signature of non-seminomas at a single-cell level, presenting a wealth of promising targets with substantial potential for informing the development of future therapeutic interventions.

Moreover, coculturing with RENCA/hCA9 cells more actively prompted T cell apoptosis than with RENCA cells. Collectively, these findings suggest hypoxia-associated CA9 not only boosts serpinB9 in cancer cells but also synergistically intensifies T cell apoptosis via acidosis, characterizing RENCA/hCA9 tumors as "cold."

In hepatoblastoma, SerpinB9 is thought to be more highly expressed in macrophages and enhanced by interaction with hepatoblastoma cell.

These findings suggest that SerpinB9 contributes to the immune escape of testicular germ cell tumors. Targeting therapy for SerpinB9 might therefore be useful in immunotherapy for testicular germ cell tumors resistant to immune checkpoint inhibitors.

We further combined CD19-CAR treatment with clinically relevant drugs and assessed how killing of lymphoma cells and expansion of T-cells was altered...We sought to improve T-cell-mediated cytotoxicity specifically in samples with high SERPINB9 expression and found that immune checkpoint inhibitors and lenalidomide enhanced expansion of CAR T-cells and increased killing of lymphoma cells. In addition, vorinostat and antibody-drug-conjugate polatuzumab vedotin specifically killed lymphoma cells without affecting T-cell expansion... This study is the first to investigate proteomic determinants of response to CD19-CAR and CD19-BsAb in B-NHL. With this approach, we identify tumorigenic Serpin B9 as mediator of resistance and provide combinatorial drug treatments to improve response to CD19-CAR. Collectively, these results may contribute to the targeted advancement of T-cell engaging therapy.