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.

Triple-negative breast cancer (TNBC) is the most aggressive and poorly treated subtype of breast cancer. Identifying novel drivers and mechanisms for tumor progression is essential for precise targeted therapy of TNBC. Immunoglobulin-like transcript 4 (ILT4; also known as LILRB2) is a classic myeloid suppressor for their activation and immune response. Our recent results found that ILT4 is also highly expressed in lung cancer cells, where it has a role in promoting immune evasion and thus tumor formation. However, the expression and function of ILT4 in breast cancer remains elusive. Here, using our patient cohort and public database analysis, we found that TNBC displayed the most abundant ILT4 expression among all breast cancer subtypes. Functionally, enriched ILT4 promoted TNBC cell proliferation, migration and invasion in vitro, as well as tumor growth and metastasis in vivo. Further mechanistic analysis revealed that ILT4 reprogrammed aerobic glycolysis of tumor cells via AKT-mTOR signaling-mediated glucose transporter 3 (GLUT3; also known as SLC2A3) and pyruvate kinase muscle 2 (PKM2, an isoform encoded by PKM) overexpression. ILT4 inhibition in TNBC reduced tumor progression and GLUT3 and PKM2 expression in vivo. Our study identified a novel driver for TNBC progression and proposed a promising strategy to combat TNBC by targeting ILT4.

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.