Possibilities of Improving the Clinical Value of Immune Checkpoint Inhibitor Therapies in Cancer Care by Optimizing Patient Selection

Iivanainen, Sanna; Koivunen, Jussi

doi:10.3390/ijms21020556

Cited by 23 publications

(15 citation statements)

References 155 publications

(180 reference statements)

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“…Immunotherapy is now standard for many malignancies. In breast cancer (BC), the checkpoint inhibitor anti‐PD‐L1, which blocks immunosuppressive effects of tumors on T cells, is available only for patients with triple‐negative PD‐L1–positive advanced BC 1 …”

Section: Figurementioning

confidence: 99%

“…In breast cancer (BC), the checkpoint inhibitor anti-PD-L1, which blocks immunosuppressive effects of tumors on T cells, is available only for patients with triple-negative PD-L1-positive advanced BC. 1 Activated αβ T-cell immunotherapy (ATI) is a nonspecific adoptive T-cell therapy using activated αβ T cells. 2 Activated αβ T-cell immunotherapy has proven effective in various malignancies without serious side effects.…”

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confidence: 99%

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A case of a patient receiving combination therapy with paclitaxel plus bevacizumab and adoptive activated αβ T‐cell immunotherapy in advanced breast cancer

Masuda

Nonami

Tanaka³

et al. 2020

Breast J

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Section: Figurementioning

confidence: 99%

mentioning

confidence: 99%

A case of a patient receiving combination therapy with paclitaxel plus bevacizumab and adoptive activated αβ T‐cell immunotherapy in advanced breast cancer

Masuda

Nonami

Tanaka³

et al. 2020

Breast J

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“…However, anti-PD-1/PD-L1 antibodies are only efficacious in a fraction of patients with certain cancers ( 5 ). PD-L1 protein expression is a predictive biomarker that has been widely used ( 6 ). CMTM6 can be used as a key regulator of PD-L1 protein in a broad range of cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Implications of Pan-Cancer CMTM6 Expression and Its Relationship with the Immune Microenvironment

Zhao

Zhang

et al. 2021

Front. Oncol.

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CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6) reportedly stabilizes programmed death-ligand 1 (PD-L1) and enhances the efficacy of immunotherapy. However, correlations between CMTM6 expression and the immune microenvironment and its prognostic value remain unknown in a variety of tumors. CMTM6 expression data were obtained from The Cancer Genome Atlas (TCGA) for 33 cancer types classified into high and low expression subgroups according to the median CMTM6 expression value. Pan-cancer analysis of CMTM6 protein expression in 20 tumor types was performed using a cohort from the Human Protein Atlas (HPA). PD-L1 protein expression data were obtained from The Cancer Proteome Atlas (TCPA) for 32 cancer types. Frequencies of CMTM6 copy number alterations and mutations were analyzed using cBioPortal. MANTIS was employed to estimate microsatellite instability in the TCGA cohort. CIBERSORT and the ESTIMATE algorithm were applied to estimate the relative fractions of infiltrating immune cell types and immune scores, respectively. Kaplan–Meier survival curve analysis was performed to assess the pan-cancer prognostic value of CMTM6.CMTM6 is heterogeneously expressed in diverse cancers. Further, the results revealed low CMTM6 mutation frequencies in multiple cancers. Among them, CMTM6 mutation frequency was the highest in uterine cancer. Additionally, CMTM6 expression was related to PD-L1 protein expression in breast invasive carcinoma, cervical squamous cell carcinoma and endocervical adenocarcinoma, cholangiocarcinoma, glioblastoma multiforme (GBM), head and neck squamous cell carcinoma, kidney renal papillary cell carcinoma, sarcoma (SARC), stomach adenocarcinoma, and uterine carcinosarcoma. Increased CMTM6 expression may be associated with increased infiltration of neutrophils in some types of cancer. Finally, pan-cancer analysis indicated that CMTM6 expression was closely related to overall survival in adrenocortical carcinoma, GBM, acute myeloid leukemia, liver hepatocellular carcinoma, mesothelioma, SARC, thymoma, and uveal melanoma. Taken together, these findings highlight that CMTM6 plays an important role in the tumor immune microenvironment, and CMTM6 has been identified to have prognostic value in some types of cancers. Thus, CMTM6 is a potential target for cancer immunotherapy and effective prognostic biomarker.

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“…Predictive factors enabling precise qualification of patients for immunotherapy have not been sufficiently defined, and expression of PD-L1 protein on tumor cells is the only validated factor used in clinical practice in the qualification of NSCLC patients to first line therapy with pembrolizumab ( 5 – 8 ). Unfortunately, only less than 50% of patients with PD-L1 expression on ≥50% of tumor cells respond to first line immunotherapy ( 9 , 10 ).…”

Section: Introductionmentioning

confidence: 99%

Tissue MicroRNA Expression as a Predictor of Response to Immunotherapy in NSCLC Patients

et al. 2021

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IntroductionExpression of PD-L1 protein on tumor cells, which is so far the only validated predictive factor for immunotherapy, is regulated by epigenetic and genetic factors. Among the most important ones that regulate gene expression are microRNAs.Materials and MethodsThe study included 60 patients with NSCLC who underwent first or second line immunotherapy with pembrolizumab or nivolumab. FFPE materials were collected before the start of immunotherapy. We examined relative expression of microRNAs (miR-141, miR-200a, miR-200b, miR-200c, miR-429, miR-508-3p, miR-1184, miR-1255a) and PD-L1 mRNA expression. Copy number variation (CNV) of PD-L1 gene by qPCR and FISH methods were assessed. Two single nucleotide polymorphisms (SNPs) in promoter region of PD-L1 gene (rs822335 and rs822336) were examined. Expression of PD-L1 protein on tumor cells was assessed by immunohistochemistry (IHC). The response rate to immunotherapy and progression free survival (PFS) measured in weeks and overall survival (OS) measured in months from the start of immunotherapy were evaluated.ResultsResponse to immunotherapy was observed in nine patients (15%, including one complete response), disease stabilization in 22 patients (36.7%), and progression in 29 patients (48.3%). Significantly higher (p=0.015) expression of miR-200b and significantly lower (p=0.043) expression of miR-429 were observed in responders compared to patients who did not respond to immunotherapy. The median PFS in the whole group of patients was 16 weeks, and the median OS was 10.5 month. In univariate analysis, the median PFS was significantly higher in patients with high miR-200b expression (HR=0.4253, 95%CI: 0.1737–1.0417, p=0.05) and high miR-508 expression (HR=0.4401, 95%CI: 0.1903–1.0178, p=0.05) and with low expression of miR-429 (HR=0.1288, 95%CI: 0.01727–0.9606, p=0.0456) compared to patients with low and high expression of these molecules, respectively. The median OS was higher in patients with low expression of miR-429 (HR=0,6288, 95%CI: 0,3053–1,2949, p=0.06) compared with patients with high expression of this microRNA. In multivariate analysis, we found that patients with PD-L1 expression on ≥1% of tumor cells compared to patients without PD-L1 expression on cancer cells had a significantly lower risk of progression (HR=0.3857, 95%CI: 0.1612–0.9226, p=0.0323) and death (HR=0.377, 95%CI: 0.1636–0.8688, p=0.022).ConclusionThe miR-200b and miR-429 molecules in tumor cells seem to have greatest impact on the effectiveness of immunotherapy in NSCLC patients.

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Possibilities of Improving the Clinical Value of Immune Checkpoint Inhibitor Therapies in Cancer Care by Optimizing Patient Selection

Cited by 23 publications

References 155 publications

A case of a patient receiving combination therapy with paclitaxel plus bevacizumab and adoptive activated αβ T‐cell immunotherapy in advanced breast cancer

A case of a patient receiving combination therapy with paclitaxel plus bevacizumab and adoptive activated αβ T‐cell immunotherapy in advanced breast cancer

Prognostic Implications of Pan-Cancer CMTM6 Expression and Its Relationship with the Immune Microenvironment

Tissue MicroRNA Expression as a Predictor of Response to Immunotherapy in NSCLC Patients

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