Clinical significance of programmed cell death-ligand 1 expression and the immune microenvironment at the invasive front of colorectal cancers with high microsatellite instability

PurposeTo investigate the status of mismatch repair (MMR) and microsatellite instability (MSI) in triple-negative breast cancer (TNBC) and to examine correlations between MMR/MSI status and clinicopathological parameters.MethodsWe retrospectively collected tissue samples from 440 patients with TNBC and constructed tissue microarrays. Protein expression of MLH1, MSH2, MSH6, and PMS2 was detected by immunohistochemistry (IHC). We also analyzed 195 patient samples using MSI polymerase chain reaction (PCR) testing. Correlations between MSI status and clinicopathological parameters and prognosis were analyzed.ResultsThe median age of the cohort was 49 years (range: 24–90 years) with a median follow-up period of 68 months (range: 1–170 months). All samples were positive for MLH1, MSH2, MSH6, and PMS2, except for one sample identified as MMR-deficient (dMMR) by IHC, with loss of MSH2 and intact MSH6 expression. MSI PCR revealed no case with high-frequency MSI (MSI-H), whereas 14 (7.2%) and 181 (92.8%) samples demonstrated low-frequency and absence of MSI events, respectively. The dMMR sample harbored low-frequency instability, as revealed by MSI PCR, and a possible EPCAM deletion in the tumor, as observed from next-generation sequencing. No correlations were detected between MMR or MSI status and clinicopathological parameters, programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) expression, or survival.ConclusionsThe incidence of dMMR/MSI-H is extremely low in TNBC, and rare discordant MSI PCR/MMR IHC results may be encountered. Moreover, MMR/MSI status may be of limited prognostic value. Further studies are warranted to explore other predictive immunotherapy biomarkers for TNBC.

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The clinical significance of programmed cell death-1 rs11568821 and interleukin-28b rs12979860 polymorphisms in autommune hepatitis

Journal of Hepatology ◽

10.1016/s0168-8278(20)31432-x ◽

2020 ◽

Vol 73 ◽

pp. S476-S477

Author(s):

Kalliopi Azariadi ◽

Nikolaos Gatselis ◽

Angeliki Lyberopoulou ◽

Pinelopi Arvaniti ◽

Asterios Saitis ◽

...

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Clinical Significance ◽

Interleukin 28B ◽

Programmed Cell Death 1

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Microsatellite Instability and Programmed Cell Death-Ligand 1 Expression in Stage II/III Gastric Cancer

Annals of Surgery ◽

10.1097/sla.0000000000002803 ◽

2019 ◽

Vol 270 (2) ◽

pp. 309-316 ◽

Cited By ~ 40

Author(s):

Yoon Young Choi ◽

Hyunki Kim ◽

Su-Jin Shin ◽

Ha Yan Kim ◽

Jinae Lee ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Death ◽

Programmed Cell Death ◽

Microsatellite Instability ◽

Stage Ii

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Immunophenotypes Based on the Tumor Immune Microenvironment Allow for Unsupervised Penile Cancer Patient Stratification

Cancers ◽

10.3390/cancers12071796 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1796 ◽

Cited By ~ 2

Author(s):

Chengbiao Chu ◽

Kai Yao ◽

Jiangli Lu ◽

Yijun Zhang ◽

Keming Chen ◽

...

Keyword(s):

T Cells ◽

Cell Death ◽

Programmed Cell Death ◽

Cytotoxic T Lymphocyte ◽

Granzyme B ◽

Expression Patterns ◽

Tumor Infiltrating Lymphocytes ◽

Immune Checkpoints ◽

Immune Microenvironment ◽

Tumor Immune Microenvironment

The tumor immune microenvironment (TIME) plays an important role in penile squamous cell carcinoma (peSCC) pathogenesis. Here, the immunophenotype of the TIME in peSCC was determined by integrating the expression patterns of immune checkpoints (programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1), cytotoxic T lymphocyte antigen 4 (CTLA-4), and Siglec-15) and the components of tumor-infiltrating lymphocytes, including CD8+ or Granzyme B+ T cells, FOXP3+ regulatory T cells, and CD68+ or CD206+ macrophages, in 178 patients. A high density of Granzyme B, FOXP3, CD68, CD206, PD-1, and CTLA-4 was associated with better disease-specific survival (DSS). The patients with diffuse PD-L1 tumor cell expression had worse prognoses than those with marginal or negative PD-L1 expression. Four immunophenotypes were identified by unsupervised clustering analysis, based on certain immune markers, which were associated with DSS and lymph node metastasis (LNM) in peSCC. There was no significant relationship between the immunophenotypes and high-risk human papillomavirus (hrHPV) infection. However, the hrHPV–positive peSCC exhibited a higher density of stromal Granzyme B and intratumoral PD-1 than the hrHPV–negative tumors (p = 0.049 and 0.002, respectively). In conclusion, the immunophenotypes of peSCC were of great value in predicting LNM and prognosis, and may provide support for clinical stratification management and immunotherapy intervention.

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Clinical significance of soluble programmed cell death ligand-1 (sPD-L1) in hepatocellular carcinoma patients treated with radiotherapy

Radiotherapy and Oncology ◽

10.1016/j.radonc.2017.11.027 ◽

2018 ◽

Vol 129 (1) ◽

pp. 130-135 ◽

Cited By ~ 23

Author(s):

Hyun Ju Kim ◽

Sangjoon Park ◽

Kyoung-Jin Kim ◽

Jinsil Seong

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Death ◽

Programmed Cell Death ◽

Clinical Significance

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Microsatellite Instability, Epstein–Barr Virus, and Programmed Cell Death Ligand 1 as Predictive Markers for Immunotherapy in Gastric Cancer

Cancers ◽

10.3390/cancers14010218 ◽

2022 ◽

Vol 14 (1) ◽

pp. 218

Author(s):

Hung-Yuan Yu ◽

Chung-Pin Li ◽

Yi-Hsiang Huang ◽

Shao-Jung Hsu ◽

Yen-Po Wang ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Death ◽

Programmed Cell Death ◽

Microsatellite Instability ◽

Progression Free Survival ◽

Negative Group ◽

Barr Virus ◽

Positive Score ◽

Epstein Barr ◽

Combined Positive Score

Immunotherapy benefits selected cases of gastric cancer (GC), but the correlation between biomarkers and prognosis is still unclear. Fifty-two patients with GC who underwent immunotherapy were enrolled from June 2016 to December 2020. Their clinical features and biomarkers—microsatellite instability-high (MSI-H), programmed cell death ligand 1 (PD-L1) combined positive score (CPS), and Epstein–Barr encoding region (EBER)—were analyzed. Eight patients had MSI-H, five patients had EBER, 29 patients had CPS ≥ 1, and 20 patients had no biomarker. The overall response rates (ORRs) of the MSI-H, EBER, PD-L1 CPS ≥ 1, and all-negative group were 75%, 60%, 44.8%, and 15%, respectively. Compared with that of the all-negative group, progression-free survival (PFS) was better in the MSI-H (p = 0.018), CPS ≥ 5 (p = 0.012), and CPS ≥ 10 (p = 0.006) groups, but not in the EBER (p = 0.2) and CPS ≥ 1 groups (p = 0.35). Ten patients had combined biomarkers, CPS ≥ 1 with either MSI-H or EBER. The ORRs were 66.7% for CPS ≥ 1 and MSI-H and 75% for CPS ≥ 1 and EBER. PFS was better in patients with combined biomarkers (p = 0.01). MSI-H, EBER, and CPS are useful biomarkers for predicting the efficacy of immunotherapy.

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