Immunological Network Signature of Naïve Non-Oncogene-Addicted Non-Small Cell Lung Cancer Patients Treated with Anti-PD1 Therapy: A Pilot Study
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients’ Characteristics
2.2. PBMC and Serum Collection
2.3. Flow Cytometry
2.4. Cytokine and Chemokine Evaluation
2.5. Hierarchical Clustering of Circulant Molecules’ Expression Profile
2.6. Differential Correlation Analysis of Multiple Clinical Conditions
3. Results
3.1. Patients’ Characteristics
3.2. Non-Responding Patients with PS > 0 Showed an Immunosuppressive Soluble Checkpoint Signature
3.3. Non-Responding Patients Showed a Pronounced Inflammatory Network
3.4. PD-L2-IL6 and PD-L2-IL10 Connections Were Inversely Correlated in Patients with PS > 0 and PS = 0
3.5. Most of the PD-L1 Connections Were Interrupted in Patients with a Favorable Prognosis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
NSCLC | Non-small cell lung cancer |
PS | Performance status |
OS | Overall survival |
TPS | Tumor proportional score |
IDO | Indoleamine 2,3-deoxygenase |
FoxO3 | Forkhead Box O3 |
EOCG | Eastern Cooperative Oncology Group |
FDR | False discovery rate |
DGCA | Different gene correlation |
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Tot | N°27 (100%) |
---|---|
Sex | |
Male | 18 (67%) |
Female | 9 (33%) |
AgeMedian range | 48–84 |
≤75 | 22 (81) |
>75 | 5 (19) |
Histotype | |
Squamous | 6 (22) |
Adenocarcinoma | 21 (78) |
TPS | |
<50% | 16 (59) |
≥50% | 11 (41) |
EOCG Performance Status | |
0 | 15 (55) |
>0 | 12 (45) |
Overall Survival | |
≤3 months | 6 (22) |
>3 months | 21 (78) |
Smoking Status | |
Current | 13 (48) |
Former | 7 (26) |
Non-smoker | 7 (26) |
Response to immunotherapy | |
Yes | 14 (52) |
No | 13 (48) |
Clinical Variables | Cluster 1 | Cluster 2 | Cluster 3 | p-Value Fisher Test | |
---|---|---|---|---|---|
Overall survival | Good | 2 | 10 | 3 | NS |
Bad | 1 | 5 | 4 | ||
Response to therapy | R | 3 | 6 | 3 | NS |
NR | 0 | 9 | 4 | ||
Performance Status | 0 | 0 | 8 | 6 | p < 0.0005 |
>0 | 3 | 7 | 1 |
Clinical Variables | Cluster 1 | Cluster 2 | p-Value Fisher Test | |
---|---|---|---|---|
Overall Survival | Good | 15 | 2 | NS |
Bad | 8 | 2 | ||
Response to therapy | R | 10 | 3 | NS |
NR | 13 | 1 | ||
Performance Status | 0 | 3 | 1 | NS |
>0 | 9 | 14 |
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Sibilio, P.; Zizzari, I.G.; Gelibter, A.; Siringo, M.; Tuosto, L.; Pace, A.; Asquino, A.; Valentino, F.; Sabatini, A.; Petti, M.; et al. Immunological Network Signature of Naïve Non-Oncogene-Addicted Non-Small Cell Lung Cancer Patients Treated with Anti-PD1 Therapy: A Pilot Study. Cancers 2025, 17, 922. https://doi.org/10.3390/cancers17060922
Sibilio P, Zizzari IG, Gelibter A, Siringo M, Tuosto L, Pace A, Asquino A, Valentino F, Sabatini A, Petti M, et al. Immunological Network Signature of Naïve Non-Oncogene-Addicted Non-Small Cell Lung Cancer Patients Treated with Anti-PD1 Therapy: A Pilot Study. Cancers. 2025; 17(6):922. https://doi.org/10.3390/cancers17060922
Chicago/Turabian StyleSibilio, Pasquale, Ilaria Grazia Zizzari, Alain Gelibter, Marco Siringo, Lucrezia Tuosto, Angelica Pace, Angela Asquino, Flavio Valentino, Arianna Sabatini, Manuela Petti, and et al. 2025. "Immunological Network Signature of Naïve Non-Oncogene-Addicted Non-Small Cell Lung Cancer Patients Treated with Anti-PD1 Therapy: A Pilot Study" Cancers 17, no. 6: 922. https://doi.org/10.3390/cancers17060922
APA StyleSibilio, P., Zizzari, I. G., Gelibter, A., Siringo, M., Tuosto, L., Pace, A., Asquino, A., Valentino, F., Sabatini, A., Petti, M., Bellati, F., Santini, D., Nuti, M., Farina, L., Rughetti, A., & Napoletano, C. (2025). Immunological Network Signature of Naïve Non-Oncogene-Addicted Non-Small Cell Lung Cancer Patients Treated with Anti-PD1 Therapy: A Pilot Study. Cancers, 17(6), 922. https://doi.org/10.3390/cancers17060922