CD8+/FOXP3+ Ratio and PD-L1 Expression Associated With Survival in pT3N0M0 Stage Esophageal Squamous Cell Cancer

Zhu, Yingming; Li, M.; Mu, Dianbin; Kong, Lingling; Zhang, J.; Zhao, Fen; Li, Z.; Liu, X.; Cong, Bin; J, Yu

doi:10.1016/j.ijrobp.2017.01.140

Cited by 11 publications

(20 citation statements)

References 29 publications

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“…On the other hand, in a recent study, PD‐L1 expression was associated with a significantly worse prognosis in patients with SCC undergoing esophagectomy or definitive radio‐chemotherapy . In a different series, in patients with SCC who underwent surgery without preoperative therapy, high PD‐L1 expression was also associated with worse overall and relapse‐free survival . On the contrary, in patients undergoing surgery alone, PD‐L1 expression was positively associated with a better prognosis .…”

Section: Discussionmentioning

confidence: 85%

PD‐L1 expression, CD8+ and CD4+ lymphocyte rate are predictive of pathological complete response after neoadjuvant chemoradiotherapy for squamous cell cancer of the thoracic esophagus

et al. 2019

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Background Neoadjuvant chemoradiotherapy (CTRT) can effectively downstage esophageal squamous cell carcinoma (SCC) in patients with locally advanced disease and prolonged survival have been observed in patients with a pathological complete response (ypCR). Aims and methods This exploratory study aimed to identify immunological predictors of pCR after neoadjuvant CTRT within SCC microenvironment. The tumor regression after neoadjuvant therapy was measured according to the Mandard score system. Eighty‐eight consecutive patients with SCC of the thoracic esophagus who received neoadjuvant CTRT were included in this retrospective study. Inclusion criteria were neoadjuvant CTRT and the availability of representative histological samples taken at diagnosis. We investigated immunohistochemical expression of CD4, Tbet, FoxP3, CD8, CD80, PD‐L1, and PD‐1, in the pretreatment biopsies and correlated the immunohistochemical profiles to patients’ outcomes. Results After neoadjuvant CTRT, 23 patients had pCR, while 65 ones had partial response, stable disease or progression. PD‐L1 expression and CD8+ and CD4+ lymphocyte rate were significantly higher in patients who had ypCR compared to those who had not (10 (0‐55) vs 0 (0‐0), P = 0.004, 73 (36‐147) vs 21 (7‐47), P = 0.0006 and 39 (23‐74) vs 5 (0‐13), P < 0.0001 respectively). The accuracy of expression of PD‐L1+, CD8+, and CD4+ lymphocyte rate in identifying responders was AUC = 0.76 (P = 0.001), AUC = 0.81 (P = 0.0001) and AUC = 0.75 (P = 0.0001), respectively. Within the ypCR group, all patients with high infiltration of CD4+ T cell recurred/relapsed while only the 38.9% of those with low CD4+ T cell infiltration did the same (P = 0.058). Conclusions PD‐L1 expression and CD8+ and CD4+ lymphocyte rate were predictive of ypCR after neoadjuvant CTRT for SCC of the thoracic esophagus with adequate accuracy. Furthermore, recurrence/relapse was associated with high level of CD4+ T cell infiltration. However, the small sample size prevented to draw definitive conclusions; further studies are necessary to evaluate the prognostic role of these markers.

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Section: Discussionmentioning

confidence: 85%

PD‐L1 expression, CD8+ and CD4+ lymphocyte rate are predictive of pathological complete response after neoadjuvant chemoradiotherapy for squamous cell cancer of the thoracic esophagus

et al. 2019

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“…Immunohistochemical PD‐1 expression on lymphocytes was associated with the peritumoral reaction in tumours. In contrast to previous studies of patients with oesophageal cancer, the present study evaluated morphological components of lymphocytic reactions in a much larger patient cohort. Given that morphological lymphocytic reactions can be assessed by routine histopathological examination of resection specimens, these observations may have clinical implications.…”

Section: Discussionmentioning

confidence: 99%

“…A question that remains unanswered is whether subtyping of infiltrating lymphocytes would provide additional information beyond morphological or histopathological evaluation of lymphocytic reaction patterns. Previous studies of oesophageal cancer have reported that the presence of infiltrates or their localization by specific subtype of lymphocytes (such as CD8+, CD57+, FOXP3+ lymphocytes) is associated with patient outcome. On the other hand, other lymphocyte subsets, including CD3+, CD4+ or CD45RO+ lymphocytes, were not associated with patient survival.…”

Section: Discussionmentioning

confidence: 99%

“…The morphological lymphocytic reaction observed by pathological examination is an indicator of the host immune response to tumour cells. The relationship between stronger lymphocytic reactions and favourable clinical outcome has been reported in some cancers, including oesophageal cancer. However, the validity of these studies was affected by small sample sizes and low statistical power.…”

Section: Introductionmentioning

confidence: 99%

“…The relationship between stronger lymphocytic reactions and favourable clinical outcome has been reported in some cancers, including oesophageal cancer. However, the validity of these studies was affected by small sample sizes and low statistical power. Importantly, the density of tumour‐infiltrating lymphocytes in the invasive margin of the tumour may predict the response to immune checkpoint inhibitors.…”

Section: Introductionmentioning

confidence: 99%

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Morphological lymphocytic reaction, patient prognosis and PD-1 expression after surgical resection for oesophageal cancer

Baba

Yagi

Kosumi

et al. 2019

British Journal of Surgery

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Background Immune checkpoint inhibitors, such as antibody against programmed cell death protein (PD‐1), have demonstrated antitumour effects in patients with malignancies, including oesophageal cancer. A lymphocytic reaction observed by pathological examination is a manifestation of the host immune response to tumour cells. It was hypothesized that a stronger lymphocytic reaction to tumours might be associated with favourable prognosis in oesophageal cancer. Methods Using a database of resected oesophageal cancers, four morphological components of lymphocytic reactions (peritumoral, intranest, lymphoid and stromal) to tumours were evaluated in relation to clinical outcome, PD‐1 expression by immunohistochemistry and total lymphocyte count in blood. Results Resected oesophageal cancer specimens from 436 patients were included in the study. Among the four morphological components, only peritumoral reaction was associated with patient prognosis (multivariable P for trend <0·001); patients with a higher peritumoral reaction had significantly longer overall survival than those with a lower reaction (multivariable hazard ratio 0·48, 95 per cent c.i. 0·34 to 0·67). The prognostic effect of peritumoral reaction was not significantly modified by other clinical variables (all P for interaction >0·050). Peritumoral reaction was associated with total lymphocyte count in the blood (P < 0·001), supporting the relationship between local immune response and systemic immune competence. In addition, higher morphological peritumoral reaction was associated with high PD‐1 expression on lymphocytes in tumours (P = 0·034). Conclusion These findings should help to improve risk‐adapted therapeutic strategies and help stratify patients in the future clinical setting of immunotherapy for oesophageal cancer.

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Predictive value of CD8/FOXP3 ratio combined with PD‐L1 expression for radiosensitivity in patients with squamous cell carcinoma of the larynx receiving definitive radiation therapy

et al. 2020

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Background: Little is known about immune-related radiosensitivity in patients with squamous cell carcinoma of the larynx (SCC-L) treated with radiation therapy (RT). Methods: We retrospectively reviewed 91 patients with SCC-L treated with RT or chemoradiation therapy and performed immunohistochemical examination to analyze PD-L1 level on tumor cells, CD4 + tumor-infiltrating lymphocytes (TILs), CD8 + TIL, and FOXP3 + TIL using pretreated biopsy specimens. The association between these immune-related parameters and radiosensitivity was evaluated. Results: Multivariate analyses showed that high CD8/FOXP3 ratio combined with negative PD-L1 expression was an independent and significant favorable predictive factor for local control, compared with the other groups. Conclusions: We showed that high CD8/FOXP3 ratio combined with negative PD-L1 expression might be a useful biomarker of radiosensitivity in patients with SCC-L receiving definitive RT. We propose that coassessment of CD8/FOXP3 ratio and PD-L1 expression level in tumor cells can help predict potential radiosensitivity in patients with SCC-L.

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CD8+/FOXP3+ Ratio and PD-L1 Expression Associated With Survival in pT3N0M0 Stage Esophageal Squamous Cell Cancer

Abstract: ABSTRACT

Cited by 11 publications

References 29 publications

PD‐L1 expression, CD8+ and CD4+ lymphocyte rate are predictive of pathological complete response after neoadjuvant chemoradiotherapy for squamous cell cancer of the thoracic esophagus

PD‐L1 expression, CD8+ and CD4+ lymphocyte rate are predictive of pathological complete response after neoadjuvant chemoradiotherapy for squamous cell cancer of the thoracic esophagus

Morphological lymphocytic reaction, patient prognosis and PD-1 expression after surgical resection for oesophageal cancer

Predictive value of CD8/FOXP3 ratio combined with PD‐L1 expression for radiosensitivity in patients with squamous cell carcinoma of the larynx receiving definitive radiation therapy

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