Kaposi Sarcoma

P3, N=130, Not yet recruiting, AIDS Malignancy Consortium | Trial completion date: Dec 2029 --> Nov 2027 | Trial primary completion date: Mar 2028 --> Dec 2026

P2, N=25, Not yet recruiting, AIDS Malignancy Consortium | Trial completion date: Aug 2029 --> Jun 2027 | Trial primary completion date: Aug 2028 --> Jun 2027

P=N/A, N=462, Completed, AIDS Malignancy Consortium | Active, not recruiting --> Completed | N=720 --> 462

The 3-years overall survival rate was 67.6%.ConclusionsThis study offers insights into cancer burden among PLWH in Turkey. High rates of ADCs and mortality highlight the importance of early HIV diagnosis and antiretroviral therapy access to reduce cancer burden in this population.

By using these TCRs transgenically expressed on T cells as identifiers for KSHV-specific cells, we show that despite their failure to recognize KSHV-infected B cells in vitro, activated effector memory differentiated LANA-specific CD4+ T cells accumulate in vivo at infection sites in the preclinical infection model of humanized mice. This suggests more efficient antigen-presentation in vivo than by KSHV-infected B cells in vitro and highlights the possible contribution of CD4+ T cells to the immunosurveillance of latently infected B cells.

PGNEA successfully identified viral infection-related pathways enriched in severe COVID-19 gene networks, including those linked to "COVID-19," "HIV-1 infection," "Hepatitis B," "Influenza A," "Measles," and "Kaposi sarcoma-associated herpesvirus infection." Notably, key molecular markers such as PIK3, NF-B family members, FOXA, JUN, and CXCL8 were identified, with strong and consistent molecular interplays between CXCL8 and NFKBIA. These findings underscore the potential of PGNEA as an efficient tool for identifying biologically meaningful pathways and network-level mechanisms associated with various phenotypes, including severe viral infections.

These results suggest that LANA TR binding establishes an enhancer domain for infected KSHV episomes. The strength of this enhancer, regulated by TR length or transcription memories from prior activation, determines the degree of KSHV lytic replication.

Our spatial transcriptomic results from thousands of spots across multiple KS tumors indicated a correlation between high levels of STC1 and decreased expression of macrophage markers. Together, these analyses offer potential mechanisms by which KSHV infection may remodel skin tissue, inhibit immune responses against KSHV infection, and confer resistance to anticancer therapies.

P1, N=56, Recruiting, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Recruiting

Interestingly, to evade this host antiviral mechanism, KSHV RTA can promote PPP2R1A degradation through ubiquitin-proteasome pathway. Taken together, we identified that the scaffold protein PPP2R1A is a new binding partner of RTA, and the interaction induces RTA dephosphorylation mediated by phosphatase PP2A, impairing KSHV lytic replication, which provide new insights into the development of novel antiviral strategies.

In this study, we developed a new mouse model to understand the B cell-intrinsic role of IL-17RA signaling in gammaherpesvirus infection. Previous studies have shown that IL-17RA signaling is proviral in the context of gammaherpesvirus infection, and this study found that while B cell-intrinsic IL-17RA signaling is not the sole factor behind the systemic proviral role of IL-17RA signaling, it plays an important role in the virus-driven germinal center response, the expansion of B-1 B cells, and the establishment of chronic gammaherpesvirus infection.

P2, N=26, Completed, AIDS Malignancy Consortium | Trial completion date: Jan 2026 --> Apr 2025 | Active, not recruiting --> Completed