Advancing clinical-basic-clinical research: exploring novel immunotargets for ovarian cancer

In a recent paper published in Cell,¹ Luo and colleagues performed a multi-omics analysis of a prospective phase II clinical trial and elucidated the effector regulatory T cells (eTregs) as novel immunotarget for ovarian cancer with homologous recombination deficiency (HRD), analyzing for the first time at the clinical level how poly (ADP-ribose) polymerase (PARP) inhibitors reshape the ovarian cancer microenvironment. The implications of targeting eTregs and combining PARP inhibitors could pave the way for more effective therapies clinically, which is also a typical example of practicing the concept of reverse transformation medicine (RTM) (Fig. 1).

Fig. 1

Schematic diagram of the clinical-basic-clinical cycle. The upper panel presents a specific case study exemplifying the integrative clinical-basic-clinical approach, which recently published in a Cell paper. a The current therapy for HRD ovarian cancer mainly includes surgery, platinum-based neoadjuvant chemotherapy and PARPi maintenance. On this basis, the authors hope to deeply analyze the unique immune profiles of the ovarian cancer tumor microenvironment and provide clues to the phenomenon that HRD tumors respond to PARPi rather than PD-1 immunotherapy. b Next, the authors pioneered a clinical trial of neoadjuvant PARPi for oral monotherapy of HRD advanced ovarian cancer (NANT, NCT04507841). c CCR8⁺ eTregs was then identified as a key responder using multi-modality profiling in clinical samples, emerging as a novel immunotarget for HRD ovarian cancer. d Anti-CCR8 mAb was successfully verified an effective immunotherapy regimen, which pave the way for the more effective therapies and improving patient outcomes combined with niraparib. e The lower panel of the diagram illustrates the cyclical loop that connects clinical practice with basic research and back to clinical application, aiming to address key biological questions and to pioneer innovative therapeutic strategies. This process concludes the main four steps: (1) discover new biological insights based on the current clinical therapy; (2) design new clinical trials according to the current unsolved research questions; (3) identify key responders using clinical samples and multi-modality profiling; (4) enlighten novel immunotargets to help develop new clinical therapy

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