Long-term outcomes of PARP inhibitors in ovarian cancer: survival, adverse events, and post-progression insights.

Poly-ADP-ribose polymerase inhibitors (PARPis) have revolutionized the management of BRCA-mutated (BRCA) and homologous recombination deficiency (HRD)-positive ovarian cancer (OC). While long-term analyses clearly support the use of PARPi as maintenance therapy after first-line chemotherapy, recent data have raised concerns on detrimental overall survival (OS) in non-BRCA OC, a greater incidence of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), and unfavorable outcomes following subsequent platinum-based chemotherapy in pretreated OC patients. In this report we discuss the long-term follow-up results from phase III trials in pretreated OC patients, which led to the Food and Drug Administration's withdrawal of PARPi indications in this setting.

Crosstalk of T cells within the ovarian cancer microenvironment.

Ovarian cancer (OC) represents ecosystems of highly diverse tumor microenvironments (TMEs). The presence of tumor-infiltrating lymphocytes (TILs) is linked to enhanced immune responses and long-term survival. In this review we present emerging evidence suggesting that cellular crosstalk tightly regulates the distribution of TILs within the TME, underscoring the need to better understand key cellular networks that promote or impede T cell infiltration in OC.

Tumor-reactive T cell clonotype dynamics underlying clinical response to TIL therapy in melanoma.

Adoptive cell therapy (ACT) using in vitro expanded tumor-infiltrating lymphocytes (TILs) has inconsistent clinical responses. To better understand determinants of therapeutic success, we tracked TIL clonotypes from baseline tumors to ACT products and post-ACT blood and tumor samples in melanoma patients using single-cell RNA and T cell receptor (TCR) sequencing. Patients with clinical responses had baseline tumors enriched in tumor-reactive TILs, and these were more effectively mobilized upon in vitro expansion, yielding products enriched in tumor-specific CD8 cells that preferentially infiltrated tumors post-ACT.

The Impact of Neoadjuvant Chemotherapy on Ovarian Cancer Tumor Microenvironment: A Systematic Review of the Literature.

Immunotherapy, particularly the use of immune checkpoint inhibitors (ICIs), has shown limited efficacy in treating ovarian cancer (OC), possibly due to diverse T cell infiltration patterns in the tumor microenvironment. This review explores how neoadjuvant chemotherapy (NACT) impacts the immune landscape of OC, focusing on tumor-infiltrating lymphocytes (TILs), PD-1/PD-L1 expression, and their clinical implications. A comprehensive literature search across four databases yielded nine relevant studies.