Pulmonary pleomorphic carcinoma treated with PD-1 inhibitor: Two case reports.

Pulmonary polymorphic carcinoma (PPC) is a rare and poorly differentiated form of non-small cell lung cancer (NSCLC), accounting for just approximately 0.1% to 0.4% of all NSCLC cases. Historically, the conventional treatments for PPC have been linked to a grim prognosis. However, with the advent of immune checkpoint inhibitors (ICIs), including PD-1 inhibitors, for the management of NSCLC, our center has witnessed encouraging outcomes in two PPC patients who underwent PD-1 inhibitor therapy. The first patient was a 70-year-old male who initially came to our attention after the discovery of a lung mass during a routine physical examination. A lung biopsy confirmed the diagnosis of PPC, and further complications included brain metastasis. Surgical intervention was conducted for the brain metastases, while PD-1 inhibitor therapy was employed for the lung tumors. The second patient was a 60-year-old male who was admitted with a history of persistent coughing and hemoptysis, which led to the diagnosis of a left lung tumor. Subsequent postoperative pathology revealed pulmonary adenocarcinoma coexisting with PPC. However, 2 months later, distant metastases were detected during a follow-up examination. The patient encountered difficulty in tolerating the adverse effects of chemotherapy, prompting the initiation of PD-1 inhibitor treatment. Notably, both patients underwent one cycle of PD-1 inhibitor therapy without encountering significant adverse reactions, and their responses proved to be promising during re-examinations. These findings suggest that surgery combined with immunotherapy PD-1 inhibitor therapy may represent an effective approach for the treatment of PPC.

Frequency changes in HLA-I alleles: A marker to guide immunotherapy in lung adenocarcinoma patients and its relationship with tumor mutational burden and PD-L1 expression.

BACKGROUND: The aim of the study was to investigate differences in HLA-I alleles between lung adenocarcinoma patients and healthy controls and determine their association with PD-L1 expression and tumor mutational burden (TMB) to understand the mechanism underlying lung adenocarcinoma susceptibility. METHODS: Differences in HLA allele frequencies between the two groups were analyzed in a case-control study. PD-L1 expression and TMB in lung adenocarcinoma patients were determined and their relationships with HLA-I were analyzed. RESULTS: The lung adenocarcinoma group showed significantly higher HLA-A*30:01 (p = 0.0067, odds ratio [OR], 1.834; 95% confidence interval [CI]: 1.176-2.860), B*13:02 (p = 0.0050, OR, 1.855; 95% CI: 1.217-2.829), and C*06:02 (p = 0.0260, OR, 1.478; 95% CI: 1.060-2.060) and significantly lower B*51:01 (p = 0.0290, OR, 0.6019; 95% CI: 0.3827-0.9467), and C*14:02 (p = 0.0255, OR, 0.5089; 95% CI: 0.2781-0.9312) than the control group. Haplotype analysis results showed that HLA-A*30:01-B*13:02 (p = 0.0100, OR, 1.909; 95% CI: 1.182-3.085), A*11:01-C*01:02 (p = 0.0056, OR, 1.909; 95% CI: 1.182-3.085), A*30:01-C*06:02 (p = 0.0111, OR, 1.846; 95% CI: 1.147-2.969), and B*13:02-C*06:02 (p = 0.0067, OR, 1.846; 95% CI: 1.147-2.969) frequencies significantly increased and B*51:01-C*14:02 (p = 0.0219, OR, 0.490; 95% CI: 0.263-0.914) frequency significantly decreased in lung adenocarcinoma patients. Three-locus haplotype analysis showed that HLA-A*30:01-B*13:02-C*06:02 frequency (p = 0.0100, OR, 1.909; 95% CI: 1.182-3.085) significantly increased in patients. CONCLUSION: HLA-A*30:01, B*13:02, and C*06:02 may be the susceptibility genes and HLA-B*51:01 and C*14:01 act as the resistance genes of lung adenocarcinoma. The changes in HLA-I allele frequencies had no association with PD-L1 expression and TMB among these patients.