Table Info

Table 2.

Research challenges and perspectives

Target	Need	Future directions
Clinical implications and challenges	PD-1/PD-L1-based immunotherapy presents challenges in managing cancer-related pain and requires attention from healthcare providers.	Developing targeted pain management strategies to improve patient care
	Patient monitoring and feedback are crucial for adjusting pain management strategies in real-time.	PROMs, PROs, and PREMs to gather data on patient experiences and outcomes
	Ameliorate diagnosis of pain phenomena (e.g., neuropathic pain)	Fostering collaboration across multidisciplinary teams to address pain management challenges
Preclinical research	Mechanisms through which PD-L1/PD-1 immunotherapy modulates pain	Developing ad hoc pain models Exploring the intersection of analgesic pathways and chronic pain processes Identifying specific mechanisms and biomarkers to guide targeted pain management
Clinical research	The link between immunotherapy and pain conditions	Comprehensive data collection, longitudinal studies EBM analyses
Artificial intelligence	Artificial intelligence can be used to: analyze large datasets, such as patient records and genomic data, to identify patterns and correlations between immunotherapy and pain; identify potential biomarkers and risk factors for pain-related complications; molecular docking; assess risk and aid in tailoring treatments; assist in making informed decisions (clinical decision support systems); simulate treatment scenarios and predict potential outcomes for improved pain management.

Addressing ethical issues and risk of bias. PD-1/PD-L1: programmed cell death-1/programmed cell death ligand-1; PROMs: patient-reported outcome measures; PROs: patient-reported outcomes; PREMs: patient-reported experiences measures; EBM: evidence-based medicine

Declarations

Acknowledgments

The TRIAL Group: Ciro Emiliano Boschetti, Alessandra Bracigliano, Giuseppe Buongiorno, Lucia Cannella, Ester Calogero, Roberta Carella, Laura Cascella, Vincenzo Cascella, Francesco Casto, Alessio Cirillo, Ottavia Clemente, Vincenzo Damiano, Matteo De Simone, Rosario De Feo, Giuseppina Della Vittoria Scarpati, Simone D’Ambrosio, Ida D’Onofrio, Morena Fasano, Giulio Ferone, Pierluigi Franco, Daria Maria Filippina, Luigi Pio Guerrera, Franco Ionna, Davide Leopardo, Francesco Longo, Maria Grazia Maglione, Roberto Manzo, Luisa Marciano, Maria Grazia Massaro, Aurora Mirabile, Massimo Montano, Costanza Pagliuca, Luca Perna, Arianna Piccirillo, Monica Pontone, Fabiana Raffaella Rampetta, Vincenzo Ricci, Lorenzo Triuzzi, Pasquale Vitale, Alessia Zotta, Antonio Grimaldi

Author contributions

M Cascella, FS, and GV: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. BM, CG, LS, MM, and LF: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. OP, SP, and FG: Validation, Writing—review & editing. FP, AO, M Capuozzo, AG, and GS: Supervision. FM and AC: Software. AM and LL: Visualization. All members of The TRIAL Group: Supervision. All authors read and approved the submitted version.

Conflicts of interest

Giustino Varrassi, the Editorial Board Member and a Guest Editor of Exploration of Immunology, had no involvement in the decision-making or the review process of this manuscript. The other authors declare no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

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