Prognostic significance of immunohistochemical classification utilizing biopsy specimens in patients with extensive-disease small-cell lung cancer treated with first-line chemotherapy and immune checkpoint inhibitors

• Published in: Journal of cancer research and clinical oncology 2024-03, Vol.150 (3), p.125-125, Article 125
• Main Authors: Shijubou, Naoki, Sumi, Toshiyuki, Kubo, Terufumi, Sasaki, Kenta, Tsukahara, Tomohide, Kanaseki, Takayuki, Murata, Kenji, Keira, Yoshiko, Terai, Kotomi, Ikeda, Tatsuru, Yamada, Yuichi, Chiba, Hirofumi, Hirohashi, Yoshihiko, Torigoe, Toshihiko
• Format: Article
• Language: English
• Subjects: ASCL1 protein; Biopsy; Cancer Research; CD8 antigen; Chemotherapy; Cytotoxicity; Hematology; Histocompatibility antigen HLA; Immune checkpoint inhibitors; Immunohistochemistry; Infiltration; Internal Medicine; Lung cancer; Lung diseases; Medicine; Medicine & Public Health; Multivariate analysis; Oncology; Patients; Small cell lung carcinoma
• ISSN: 1432-1335; 0171-5216; 1432-1335
• DOI: 10.1007/s00432-024-05652-2

Purpose Although immune checkpoint inhibitors (ICIs), together with cytotoxic chemotherapy (chemoimmunotherapy), have been adapted for the initial treatment of extensive-disease small-cell lung cancer (ED-SCLC), they have achieved limited success. In ED-SCLC, a subtype of SCLC, the expression of immune-related molecules and clinical data are not well understood in relation to ICI treatment efficiency. Methods We examined lung biopsy specimens from patients diagnosed with ED-SCLC treated with chemoimmunotherapy or chemotherapy. SCLC subtype, expression of HLA class I, and infiltration of CD8-positive cells were examined using immunohistochemistry (IHC). Subsequently, the association between clinical factors, IHC results, and progression-free survival or overall survival was assessed. Results Most of the cases showed the achaete-scute homolog 1 (ASCL1) subtype. Among the 75 SCLC cases, 29 expressed high levels of HLA class I, while 46 showed low levels or a negative result; 33 patients were characterized as CD8-high, whereas 42 were CD8-low. In the chemoimmunotherapy cohort, multivariate analysis revealed a correlation between CD8-high and improved survival. Specifically, patients in the CD8-high group of the chemoimmunotherapy cohort experienced enhanced survival compared to those in the chemotherapy cohort, which was attributed to ICI addition. IHC subtype analysis demonstrated a survival advantage in the SCLC-I and SCLC-A groups when ICI was combined with chemotherapy compared to chemotherapy alone. Conclusion Our study highlights the predictive value of IHC-classified subtypes and CD8-positive cell infiltration in estimating outcomes for patients with ED-SCLC treated with chemoimmunotherapy as a first-line therapy. These findings have practical implications for daily clinical assessments and treatment decisions.