Surgical Resection of SCLC: Prognostic Factors and the Tumor Microenvironment

Zhao, Xiaoliang; Kallakury, Bhaskar; Chahine, Joeffrey J.; Hartmann, D.; Zhang, Yuwen; Chen, Yulong; Zhang, Hua; Zhang, Bin; Wang, Changli; Giaccone, Giuseppe

doi:10.1016/j.jtho.2019.01.019

Cited by 72 publications

(71 citation statements)

References 41 publications

(53 reference statements)

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“…As for other factors, the results were consistent with ours. CD3 TILs were associated with a good prognosis [48,49]. CD4 TILs in the area of B-cell diffuse large-cell Non-Hodgkin Lymphoma (NHL) predicted a better prognosis [36].…”

Section: Discussionmentioning

confidence: 99%

Expression and clinical significance of human leukocyte antigen class II, PD-1/PD-L1, and immune cells in small cell lung cancer

Zhang

et al. 2020

Preprint

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Background Human leukocyte antigen class II (HLA class II) is considered to be related to antitumor immunity. But its value in SCLC is still unclear. In this study, we analyzed HLA class II, programmed death receptor-1/programmed death receptor-1 (PD-1/PD-L1), and immune cells (CD3, CD4, CD8, FOXP3) expression and their role in predicting the patient’s prognosis in SCLC. Methods We analyzed 102 surgical SCLC tumor samples from Shanghai Pulmonary Hospital, China. HLA class II was detected by immunohistochemistry (IHC), and we analyzed the status of HLA class II protein expressed in SCLC. Correlation between HLA class II and PD-1/PD-L1, immune cells, clinicopathological variables, and the survival data were also studied. Results 44.1% of patients expressed HLA class II on tumor-infiltrating lymphocytes (TILs) positively, yet only 5.9% of patients expressed it on SCLC tumor cells. HLA class II on TILs was positively related to PD-1, PD-L1 on TILs, and immune cells. On tumor cells, it also had a positive relationship with PD-1 on TILs (correction coefficient = 0.723, p = 0.006). Comparison of logistic regression models indicates that the odds ratios (ORs) for expression of HLA II on TILs were 3.233 (95% CI: 1.051 ~ 9.95, p = 0.041) when negative for PD-L1 on TILs were compared with those positive for PD-L1 on TILs, and 0.314 (95% CI: 0.118 ~ 0.838, p = 0.021) when negative lymph node metastasis was compared with that positive one. With the Cox regression model, the stage, HLA class II on TILs, PD-L1 on TILs, CD3, CD4, CD8, FOXP3 were considered as protective factors for relapse-free survival (RFS). HLA class II positive patients had a longer RFS (1.20 years, 95% CI: 0.83 ~ 1.57 versus. 3.40 years, 95% CI: 2.47 ~ 4.33, p = 0.015). The high level of HLA class II expressed on TILs was related to a better prognosis. The RFS of patients with positive HLA class II, PD-1/PD-L1, and immune cells was higher than that of these all negative patients (3.45 years, 95% CI: 2.92 ~ 3.97 versus. 2.02 years, 95% CI: 1.32 ~ 2.72, p = 0.001). Conclusions HLA class II was expressed on SCLC TILs, which was correlated with PD-1/PD-L1 and immune cells expression. HLA class II positive patient had a better prognosis.

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Section: Discussionmentioning

confidence: 99%

Expression and clinical significance of human leukocyte antigen class II, PD-1/PD-L1, and immune cells in small cell lung cancer

Zhang

et al. 2020

Preprint

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“…Chenesseau et al [26] demonstrated the importance of lymphadenectomy for prognosis. Zhao et al [27] found that the lymph node metastasis rate was an independent factor affecting prognosis, and stage IIB and IIIA SCLC patients with negative lymph nodes had a better prognosis. Some studies also suggested that in both NSCLC and SCLC, subcarinal lymph node metastasis is an independent factor affecting prognosis [28,29].…”

Section: Survival Analysismentioning

confidence: 99%

“…Two recent studies that included the data of surgically treated SCLC patients in the SEER database from 2010 to 2015 and from 2004 to 2015, respectively, found that postoperative adjuvant chemotherapy and radiotherapy improved the prognosis of patients [14,32]. However, another single-centre retrospective study involving 205 surgically treated SCLC patients found that postoperative adjuvant radiotherapy did not improve the prognosis of stage I-III SCLC patients [27]. Engelhardt et al [33] also found that SCLC patients did not bene t from postoperative adjuvant radiotherapy.…”

Section: Survival Analysismentioning

confidence: 99%

Clinical Outcomes and Prognosis of Small-Cell Lung Cancer(SCLC) Patients After Surgery: a Single-Centre Retrospective Cohort Study from Peking Union Medical College Hospital

Chen¹,

Liu²,

Tian³

et al. 2020

Preprint

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Background: Small-cell lung cancer (SCLC) patients are generally not considered to be candidates for surgical intervention. The role of surgery in the multidisciplinary treatment of SCLC remains controversial. The study aims to summarize and analyse the clinical characteristics and prognosis of SCLC patients after surgical treatment and identify the related prognostic factors.Methods: The clinical data of 130 SCLC patients (99 males and 31 females) who were treated by surgery and confirmed by postoperative pathological examination in Peking Union Medical College Hospital from April 2004 to April 2019 were analysed retrospectively.Results: The median age was 60 years (30-83 years), and the median disease duration was 2 months (0.5-48 months). The patients did not have specific clinical or imaging manifestations. Postoperative pathological examination revealed that 36 patients had stage I, 22 patients had stage II, 65 patients had stage III, and seven patients had stage IV SCLC. The median overall survival time was 50 months (95% confidence interval, 10.8-89.2 months). The median survival time of stage I, II, III, and IV SCLC patients were 148 months, 42 months, 32 months, and 10 months, respectively. In patients who underwent surgical treatment, postoperative adjuvant therapy and tumour stage were two significant influencing factors of survival (Cox multivariate analysis P < 0.05).Conclusions: Surgical treatment combined with adjuvant therapy can achieve satisfactory outcomes in selected SCLC patients. Adjuvant therapy and tumour stage are independent risk factors. Surgical treatment is indicated in SCLC patients preoperatively staged as I-IIIa, and anatomical lobectomy and lymphadenectomy combined with postoperative adjuvant therapy are recommended.

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“…T cells are the main component of the anticancer immune system, reflecting the immune status. Immune cell infiltration has been suggested as a key determinant of long‐term survival in SCLC, and the percentage of CD3 + T cells is an independent prognostic factor for immunotherapy . Moreover, biomarkers in the peripheral blood also predict clinical outcomes of immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

“…Immune cell infiltration has been suggested as a key determinant of long-term survival in SCLC, 11 and the percentage of CD3 + T cells is an independent prognostic factor for immunotherapy. 12 Moreover, biomarkers in the peripheral blood also predict clinical outcomes of immunotherapy. The distribution of peripheral lymphocyte subsets reflects the immune status and is correlated with survival in SCLC.…”

Section: Introductionmentioning

confidence: 99%

Pegylated recombinant human granulocyte colony‐stimulating factor regulates the immune status of patients with small cell lung cancer

et al. 2020

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Background Small cell lung cancer (SCLC) is an aggressive disease involving immunodeficiency for which chemotherapy is the standard treatment. Pegylated recombinant human granulocyte colony‐stimulating factor (PEG‐rhG‐CSF) is widely used for primary or secondary prophylaxis of febrile neutropenia (FN) in chemotherapy. However, whether PEG‐rhG‐CSF influences immune cells, such as lymphocytes, remains unclear. Methods A total of 17 treatment‐naïve SCLC patients were prospectively enrolled and divided into the PEG‐rhG‐CSF and control groups according to their FN risk. Longitudinal sampling of peripheral blood was performed before, after and 4–6 days after the first cycle of chemotherapy. Flow cytometry was used to assess lymphocyte subsets, including CD3+ T, CD4+ T, CD8+ T, NK, and B cells. The diversity and clonality of the T‐cell receptor (TCR) repertoire was analyzed by next‐generation sequencing. Results In the PEG‐rhG‐CSF group, the proportions of CD3+ T and CD4+ T cells had increased significantly (P = 0.002, P = 0.020, respectively), whereas there was no increase in CD8+ T cells. Further, TCR diversity increased (P = 0.009) and clonality decreased (P = 0.004) significantly after PEG‐rhG‐CSF treatment. However, these factors showed opposite trends before and after chemotherapy. Vβ and Jβ gene fragment types, which determine TCR diversity, were significantly amplified in the PEG‐rhG‐CSF group. The change in TCR diversity was significantly correlated with changes in the CD3+ T or CD4+ T cell proportions, but not the CD8+ T cell proportion. Conclusions PEG‐rhG‐CSF regulates the immune status of SCLC patients; CD4+ T cells may be the main effector cells involved in this process. These findings may optimize the treatment of SCLC. Key points PEG‐rhG‐CSF regulates SCLC immunity. PEG‐rhG‐CSF increased CD3+ T and CD4+T cell proportions. PEG‐rhG‐CSF increased TCR diversity and decreased clonality in peripheral blood. Change in TCR diversity were correlated with CD3+ T or CD4+ T changes.

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Surgical Resection of SCLC: Prognostic Factors and the Tumor Microenvironment

Cited by 72 publications

References 41 publications

Expression and clinical significance of human leukocyte antigen class II, PD-1/PD-L1, and immune cells in small cell lung cancer

Expression and clinical significance of human leukocyte antigen class II, PD-1/PD-L1, and immune cells in small cell lung cancer

Clinical Outcomes and Prognosis of Small-Cell Lung Cancer(SCLC) Patients After Surgery: a Single-Centre Retrospective Cohort Study from Peking Union Medical College Hospital

Pegylated recombinant human granulocyte colony‐stimulating factor regulates the immune status of patients with small cell lung cancer

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