Purpose: To compare the risk of immune-associated pneumonitis between PD-1 and PD-L1 inhibitors, the meta-analysis was designed. Method: The difference in risk of immune-associated pneumonitis between PD-1 and PD-L1 inhibitors was assessed by two different meta-analysis methods, the Mirror-pairing and the PRISMA guidelines. Results: A total of eighty-eight reports were used for meta-analysis, while thirty-two studies were used for the Mirror-pairing. Both PD-1 and PD-L1 inhibitors (used alone or combined with chemotherapy) increased the risk of developing immune-related pneumonitis (P < 0.00001; P < 0.00001). Based on indirect analyses results (subgroup analyses), the risk of PD-L1-induced pneumonitis was weaker than that of PD-1 inhibitors when the control group was chemotherapy (OR = 3.33 vs. 5.43) or placebo (OR = 2.53 vs. 3.19), while no obvious significant differences were found (P = 0.17; P = 0.53). For the Mirror-pairing-based meta-analysis, the risk of PD-1-induced pneumonitis was significantly higher than that of PD-L1 inhibitors (OR = 1.46, 95%CI [1.08, 1.98], I² = 0%, Z = 2.47 (P = 0.01)). However, this difference was not significant, when they were combined with chemotherapy (OR = 1.05, 95%CI [0.68, 1.60], I² = 38%, Z = 0.21 (P = 0.84)). Conclusion: Both PD-1 and PD-L1 inhibitors increased the risk of immune-related pneumonitis, while the risk of PD-1-induced pneumonitis was significantly higher than that of PD-L1 inhibitors.

Background. Given that immune-related rash was the most frequently reported PD-1 or PD-L1-related skin toxicity, this systematic review and meta-analysis were conducted to elucidate its incidence risk. Methods. The meta-analysis was carried out according to the PRISMA guidelines. The random effect model was used in the process of all analyses. Skin rash of all grades and grades 3–5 were calculated and gathered in the final comprehensive analyses. Results. The study included 86 clinical trials classified into 15 groups. Compared with chemotherapy, PD-1 or PD-L1 inhibitors significantly strengthened the risk of developing rash across all grades (OR = 1.66, 95% CI: [1.31, 2.11]; ). This trend was significantly stronger when the control group was placebo (OR = 2.62, 95% CI: [1.88, 3.65]; ). Similar results were observed when PD-1 or PD-L1 inhibitors were given together with chemotherapy (OR = 1.87, 95% CI: [1.59, 2.20]; ), even in patients with grades 3–5. As with other combination therapies, the risk of developing rash for all grades was enhanced when PD-1 or PD-L1 was given together with chemotherapy as the second-line option (OR = 2.98, 95% CI: [1.87, 4.75]; ). No statistically significant differences could be found in skin rash between the PD-1 and PD-L1-related subgroups. Conclusion. Whether PD-1 or PD-L1 inhibitors were given alone or together with others, the risk of developing rash would be enhanced. Furthermore, the risk of developing rash appeared to be higher when PD-1 or PD-L1 inhibitors together with other antitumor drugs were given as the second-line options. No statistically significant results of developing rash between PD-1 and PD-L1 subgroups were obtained owing to the participation of PD-1 or PD-L1 inhibitors.

Podoplanin and fibroblast growth factor (FGF) 1 have been detected more frequently in lung squamous cell carcinoma (SQCC) compared with lung adenocarcinoma. Furthermore, it has been previous demonstrated that FGF1 is located on the edge of tumor nests in certain lung SQCC sections, which resembles the characteristic expression pattern of podoplanin. Podoplanin and FGF1 have roles in lymphangiogenesis and angiogenesis. Based on their consistently specific expression in lung SQCC and similar localization patterns, the present study aimed to investigate whether the expression of podoplanin in tumor cells is correlated with FGF1 expression in lung SQCC and whether their co‑expression has clinicopathological significance, particularly for lymphangiogenesis/angiogenesis. The correlation between podoplanin and FGF1 expression in tumor cells of 82 lung SQCC cases was investigated by immunohistochemical staining and the association between the co‑expression of podoplanin and FGF1, and clinicopathological factors such as microvessel density (MVD), was examined in these samples. In addition, the prognostic value of co‑expression of podoplanin and FGF1 in tumor cells was determined, and the regulation of FGF1 expression and angiogenesis by podoplanin was examined in vitro in a human lung SQCC cell line. Immunohistochemical analysis demonstrated that there was a significant correlation between podoplanin and FGF1 expression in lung SQCC tumor cells (R=0.591; P<0.0001). Co‑expression of podoplanin and FGF1 was significantly associated with larger primary tumor size, advanced TNM stage and higher intratumoral MVD. Survival analysis demonstrated that cases with podoplanin and FGF1 double‑positive staining had a significantly lower survival rate compared with cases with double‑negative staining. In vitro experiments revealed that podoplanin regulated FGF1 expression and affected tube formation of human umbilical vein endothelial cells. Combined, the results demonstrated that podoplanin was co‑expressed with FGF1 in lung SQCC and this co‑expression was correlated with poor prognosis.

Rationale: Nuclear protein in testis carcinoma (NC) is a rare, aggressive, poorly differentiated squamous cell carcinoma. By reviewing the entire treatment process of the patient, we aim to explore the treatment experience of NC. Patient concerns: We report the case of a 27-year-old female patient with NC whose initial symptoms were occasional cough and chest tightness with abdominal distension for more than half a month without any other specific discomfort. Diagnoses: Computed tomography showed right lung hilar and right middle and lower lobe mass, malignant, right hilar and mediastinal lymph node metastasis, and bilateral cystic solid masses in the adnexal region, malignant possibility. Pathological diagnosis showed nuclear protein in the testis (+). Interventions: After the failure of first-line chemotherapy with immunocombination, second-line chemotherapy was switched to bevacizumab, which resulted in a progression-free survival of 6 months. Outcomes: The disease then reprogressed, and she died on November 7, 2022. Lessons: The patient achieved survival of nearly 1 year on multiple courses of therapy, well beyond the currently reported median survival. The patient achieved a 6-month progression-free survival, suggesting that combination therapy with antivascular endothelial growth factor class-targeted agents is a potential approach.