Clinical and prognostic implications of CD47 and PD-L1 expression in surgically resected small-cell lung cancer

Lang, Christian; Lantos, András; Egger, F.; Hoda, Mir Alireza; Mosleh, B.; Klikovits, Thomas; Oberndorfer, Felicitas; Timelthaler, G.; Ferencz, Bence; Fillinger, János; Schwendenwein, Anna; Querner, Alessandro Saeed; Boettiger, Kristiina; Rényi-Vámos, F; Höetzenecker, Konrad; László, Viktória; Schelch, Karin; Döme, Balázs

doi:10.1016/j.esmoop.2022.100631

Cited by 10 publications

(5 citation statements)

References 54 publications

(58 reference statements)

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“…Moreover, positive PD-L1 expression was evident in the tumor stroma in roughly 60% of cases, contributing significantly to a favorable impact on patient prognosis. Importantly, the authors did not discern a noteworthy correlation between PD-L1 expression and molecular subtypes of SCLC [ 44 ]. Yu et al investigated the correlation between PD-L1 expression in SCLC and its anatomical locations (central and peripheral tumor regions) as well as the expression of TTF-1 (positive and negative expression).…”

Section: Discussionmentioning

confidence: 99%

CD3, CD8, IFN-γ, tumor and stroma inflammatory cells as prognostic indicators for surgically resected SCLC: evidences from a 10-year retrospective study and immunohistochemical analysis

Fu,

Feng,

Wang

et al. 2024

Clin Exp Med

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Current clinical guidelines limit surgical intervention to patients with cT1-2N0M0 small cell lung cancer (SCLC). Our objective was to reassess the role of surgery in SCLC management, and explore novel prognostic indicators for surgically resected SCLC. We reviewed all patients diagnosed with SCLC from January 2011 to April 2021 in our institution. Survival analysis was conducted using the Kaplan–Meier method, and independent prognostic factors were assessed through the Cox proportional hazard model. In addition, immunohistochemistry (IHC) staining was performed to evaluate the predictive value of selected indicators in the prognosis of surgically resected SCLC patients. In the study, 177 SCLC patients undergoing surgical resection were ultimately included. Both univariate and multivariate Cox analysis revealed that incomplete postoperative adjuvant therapy emerged as an independent risk factor for adverse prognosis (p < 0.001, HR 2.96). Survival analysis revealed significantly superior survival among pN0-1 patients compared to pN2 patients (p < 0.0001). No significant difference in postoperative survival was observed between pN1 and pN0 patients (p = 0.062). Patients with postoperative stable disease (SD) exhibited lower levels of tumor inflammatory cells (TIC) (p = 0.0047) and IFN-γ expression in both area and intensity (p < 0.0001 and 0.0091, respectively) compared to those with postoperative progressive disease (PD). Conversely, patients with postoperative SD showed elevated levels of stromal inflammatory cells (SIC) (p = 0.0453) and increased counts of CD3+ and CD8+ cells (p = 0.0262 and 0.0330, respectively). Survival analysis indicated that high levels of SIC, along with low levels of IFN-γ+ cell area within tumor tissue, may correlate positively with improved prognosis in surgically resected SCLC (p = 0.017 and 0.012, respectively). In conclusion, the present study revealed that the patients with pT1-2N1M0 staging were a potential subgroup of SCLC patients who may benefit from surgery. Complete postoperative adjuvant therapy remains an independent factor promoting a better prognosis for SCLC patients undergoing surgical resection. Moreover, CD3, CD8, IFN-γ, TIC, and SIC may serve as potential indicators for predicting the prognosis of surgically resected SCLC.

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Section: Discussionmentioning

confidence: 99%

CD3, CD8, IFN-γ, tumor and stroma inflammatory cells as prognostic indicators for surgically resected SCLC: evidences from a 10-year retrospective study and immunohistochemical analysis

Fu,

Feng,

Wang

et al. 2024

Clin Exp Med

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“…Además, varios factores de transcripción y genes relacionados con la señalización celular, incluyendo PEA3, ETV4, ETV5, LCP2, CD47, SOX2, RUNX1T1, TEAD4 y ASXL3, también presentaron una alta expresión implicada en la progresión y recaída del cáncer, así como en la resistencia al tratamiento con inhibidores de la proteína LSD1 en el caso de TEAD4, lo que hizo que fueran catalogados por los autores como potenciales objetivos terapéuticos (11,19,20,21,28) .…”

Section: Discussionunclassified

“…Mal pronóstico de supervivencia Westerman et al, 2007 (18) CD47 Aumento de la concentración de calcio intracelular Alta Mal pronóstico de supervivencia Lang et al, 2022 (19) SOX2 Mantenimiento de la auto-renovación de las células madre embrionarias no diferenciadas Alta Aumento de la proliferación celular Tenjin et al, 2020 (20) Cui, et al 2020 (21) LSD1 Regulador de la transcripción Alta Resistencia al tratamiento quimioterapeútico Jotatsu et al, 2016 (22) Mohammad et al, 2015 (23) Nguyen. 2022 (24)…”

Section: Altaunclassified

Genes diferencialmente expresados en cáncer de pulmón de células pequeñas: Potenciales dianas terapéuticas

Jiménez Sánchez

2024

Ars Pharm

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Introducción: El cáncer de pulmón de células pequeñas (SCLC, por sus siglas en inglés) se caracteriza por una expectativa de vida desalentadora y una limitación en las opciones de tratamiento, por lo que la urgencia de encontrar nuevas dianas terapéuticas es considerable. En este contexto, la utilización de los análisis de expresión génica diferencial en células tumorales de SCLC ha permitido identificar genes anormalmente expresados que se asocian con el desarrollo y progresión de la enfermedad, lo cual puede contribuir al descubrimiento de potenciales dianas terapéuticas. Método: Se realizó una revisión bibliográfica en las bases de datos PubMed, Science Direct, Google Scholar y Wiley, tras la cual se incluyeron 28 referencias. Resultados: El análisis de la literatura reveló 37 genes diferencialmente expresados en SCLC involucrados en funciones biológicas críticas como la regulación del ciclo celular, señalización, transcripción y desarrollo embrionario. La expresión anormal de estos genes está asociada con consecuencias clínicas graves, como mal pronóstico, progresión del cáncer y resistencia a fármacos, resaltando el potencial de estos genes como posibles objetivos terapéuticos. Conclusión: La comprensión detallada de la expresión génica diferencial en SCLC abre caminos prometedores para el desarrollo de terapias dirigidas y la identificación de estos genes anormalmente expresados como potenciales dianas terapéuticas representa un enfoque prometedor en la lucha contra esta forma letal de cáncer de pulmón.

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“…Although certain molecular subtypes comprise only few patients, such as Her2 (3%), MET (3%), RET (1%), and ROS1 (1%), targeted therapy may offer significant benefits for them [ 32 ]. Similarly, small cell lung cancer is no longer considered a homogenous group, since four molecular subgroups have been discovered, which also have major therapeutic implications [ 33 , 34 ]. The different PD-L1 and PD-1 expression levels in MEC and ACC tumors found in our study raise the possibility of heterogeneity in these groups, too, which seems to be supported by recent molecular genetic studies in salivary gland ACC [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

PD-1 and PD-L1 expression in rare lung tumors

Gyulai

Reiniger

Harkó

et al. 2023

Pathol. Oncol. Res.

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Background: Our knowledge is still limited about the characteristics and treatment of rare lung tumors. The aim of our study was to determine programmed cell death ligand-1 (PD-L1) and programmed cell death-1 (PD-1) expression in rare pulmonary tumors to assess the potential role of immunotherapy.Methods: 66 pathologically confirmed rare lung tumors including 26 mucoepidermoid carcinomas (MECs), 27 adenoid cystic carcinomas (ACCs), and 13 tracheobronchial papillomas (TBPs) were collected retrospectively. Immunohistochemical (IHC) staining was performed on formalin fixed paraffin embedded (FFPE) tumor tissues, and PD-L1 expression on tumor cells (TCs) and immune cells (ICs), and PD-1 expression on ICs were determined. The cut off value for positive immunostaining was set at 1% for all markers.Results: PD-L1 expression on TCs was observed in two cases of MEC (7.7%), one case of ACC (3.7%), and was absent in TBP samples. PD-L1 expression on ICs could be demonstrated in nine cases of MEC (34.6%), four cases of ACC (14.8%), and was absent in TBPs. All PD-L1 TC positive tumors were also PD-L1 IC positive. Higher expression level than 5% of PD-L1 TC and/or IC was observed only in one ACC and in two MEC patients. Among them, strong PD-L1 immunopositivity of >50% on TCs and of >10% on ICs could be demonstrated in one MEC sample. PD-L1 expression of ≥1% on ICs was significantly more common in MEC, than in TBP (p < 0.001). In MEC ≥1% PD-L1 TC or IC expressions were significantly more common in patients aged 55 or older, than in younger patients (p = 0.046, and p = 0.01, respectively). PD-1 expression on ICs was found in five cases of MEC (19.2%), four cases of ACC (14.8%), and in two cases of TBP (15.4%). Only one MEC case showed a higher than 5% expression level of PD-1 on ICs.Conclusion: This retrospective study comprehensively demonstrated the rare expression of PD-L1 and PD-1 in pulmonary MEC, ACC, and TBP. However, we found very strong PD-L1 immunopositivity on both TCs and ICs in one MEC sample, which warrants further investigations in a larger cohort.

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Clinical and prognostic implications of CD47 and PD-L1 expression in surgically resected small-cell lung cancer

Cited by 10 publications

References 54 publications

CD3, CD8, IFN-γ, tumor and stroma inflammatory cells as prognostic indicators for surgically resected SCLC: evidences from a 10-year retrospective study and immunohistochemical analysis

CD3, CD8, IFN-γ, tumor and stroma inflammatory cells as prognostic indicators for surgically resected SCLC: evidences from a 10-year retrospective study and immunohistochemical analysis

Genes diferencialmente expresados en cáncer de pulmón de células pequeñas: Potenciales dianas terapéuticas

PD-1 and PD-L1 expression in rare lung tumors

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