PD-L1 protein expression in tumour cells and immune cells in mismatch repair protein-deficient and -proficient colorectal cancer: the foundation study using the SP142 antibody and whole section immunohistochemistry

Jabbour, Tony El; Ross, Jeffrey S.; Sheehan, Christine E.; Affolter, Kajsa; Geiersbach, Katherine B.; Boguniewicz, Ann; Ainechi, Sanaz; Bronner, Mary P.; Jones, David; Lee, Hwajeong

doi:10.1136/jclinpath-2017-204525

Cited by 22 publications

(17 citation statements)

References 37 publications

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“…In a study on lung adenocarcinoma, a correlation between high histological differentiation and PD-L1 expression on TCs and IECs was found [17]. Jabbour et al found a correlation between PD-L1 expression on TCs and IECs and tumor advancement [18]. However, other studies did not confirm these findings [19] in line with our own results.…”

Section: Discussioncontrasting

confidence: 48%

The type of distribution of PD-L1 positive immune cells and PD-L1 expression in tumor cells correlate with the development of non-classical differentiation in urinary bladder cancer

Matusiak¹,

Starzyński²,

Jóźwicki

et al. 2019

Medical Research Journal

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Background: The basic diagnostic tool of urinary bladder cancer is the histopathological assessment. However, it is insufficient to accurately predict the progression of this disease. There is a need to look for new prognostic factors that will make the therapeutic process more effective. The aim of this study is to evaluate the effect of activation of a PD1-PD-L1 immune checkpoint in immune effector cells (IECs) and tumor cells, on the development of malignancy in the form of non-classic differentiation in urinary bladder cancer. Materials and methods: 110 patients with stage pT1-pT4 urothelial bladder carcinoma who underwent radical cystectomy/cystoprostatectomy between 2011 and 2014 were included in the study. Tumor advancement (pT stage), grade (G), as well as, non-classic differentiation frequency and number were evaluated pathologically. In each case, the area of the tumor containing PD-L1+ IECs was analyzed. The distribution of PD-L1+ immune effector cells within the tumor was also assessed as dispersed or aggregated. Results: The frequency of non-classic differentiation was significantly lower in urothelial bladder cancer tumors with a dispersed pattern of distribution of PD-L1+ IECs. A correlation between the extent of PD-L1 expression in tumor cells and the non-classic differentiation number in UBC was identified. Conclusions: The distribution of cells expressing the immune checkpoint biomarker PD-L1 constitutes a new prognostic factor and may play a key role in the selection of individualized immunotherapy. In addition, the evaluation of non-classic differentiation in the tumor may complement the assessment of PD-L1 expression due to its capacity to characterize the current malignant potential of the tumor, whereas the assessment of extent and distribution of PD-L1+ in tumor-associated immune cells indicates the functional status of the immune system.

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Section: Discussioncontrasting

confidence: 48%

The type of distribution of PD-L1 positive immune cells and PD-L1 expression in tumor cells correlate with the development of non-classical differentiation in urinary bladder cancer

Matusiak¹,

Starzyński²,

Jóźwicki

et al. 2019

Medical Research Journal

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“…We used the latter value for the objective difficulties in the detection of very rare positive neoplastic cells and to avoid overestimating of PD-L1 expression. In addition, like few other studies [ 39 – 41 ], we evaluated PD-L1 not only in neoplastic cells but also in immune cells.…”

Section: Discussionmentioning

confidence: 99%

PD-L1 expression in colorectal cancer defines three subsets of tumor immune microenvironments

et al. 2018

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ObjectivesWe investigated the PD-L1 expression in colorectal cancer (CRC) and in its microenvironment.ResultsPD-L1 was expressed in neoplastic cells (NCs) and tumor-infiltrating immune cells (IICs). All samples PD-L1+ on NCs were also on IICs. Three types of cancers could be grouped: group A(NCs-/ IICs-); group B (NCs-/ IICs+); group C (NCs+/IICs+). To group A belong tumors characterized by poorly immunogenic competence, poor immune response but massive granulocyte infiltrate, justifying the absence of PD-L1 as an immunoinhibitor receptor. To Group B probably belong more immunogenic CRCs, justifying the strong IICs-mediated immune response, and up-regulation of PD-L1 expression only on IICs. To group C belong CRCs probably characterized by a large amount of tumor neoantigens resulting in a marked infiltration of lymphocytes and PD-L1 upregulation also in NCs.Materials and MethodsSixty-three colorectal cancer specimens from a cohort of 61 patients were retrospectively reviewed. Thirty-seven MSS and 26 MSI-H CRCs enrolled in this study. Immunohistochemical staining to PD-L1 was performed by using MAb E1L3N.ConclusionsOur study calls attention to the importance to assess PD-L1 expression in tumor microenvironment also evaluating type and density of infiltrating immune cells to better stratify CRCs with different immunological patterns.

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“…Some patients would benefit from PD‐1/L1, even if their PD‐L1 are negatively expressed. Predictive markers for PD‐1/L1 inhibitors are not just limited to PD‐L1 expression such as microsatellite instability, tumor mutation burden, DNA mismatch repair, T cell receptors sequencing and so forth. Except for that, many genes or mRNA base model also claimed for its predictive value in immune therapeutic efficacy, but up to now, how to accurately select patients that would benefit from immune therapy remains a complex project.…”

Section: Discussionmentioning

confidence: 99%

PD‐(L)1 inhibitors vs. chemotherapy vs. their combination in front‐line treatment for NSCLC: An indirect comparison

Liang

Liu

Pan

et al. 2019

Intl Journal of Cancer

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We comprehensively compared the therapeutic effects and safety of PD-1/L1 antibodies (I), chemotherapy (C) or their combination (I + C) as first-line treatments for advanced NSCLC. Online databases were searched to identify RCTs. Survival outcomes and safety events were pooled by indirect treatment comparison. Main subgroup analyses were conducted according to PD-L1 expression. A total of 11 RCTs involving 6,731 patients were included. Overall, PD-1/L1 inhibitors showed no difference to chemotherapy in PFS (HR 0.90, 0.65-1.24) and OS (HR 0.84, 0.64-1.09), while I + C was superior to chemotherapy both in PFS (HR 0.64, 0.58-0.71) and OS (HR 0.74, 0.62-0.89). I + C also showed advantages over PD-1/L1 in PFS (HR 0.71, 0.51-0.99) but not OS (HR 0.88, 0.64-1.22). In the PD-L1 < 1% subgroup, I + C was beneficial both in OS (HR 0.78, 0.67-0.90) and PFS (HR 0.72, 0.65-0.80) than chemotherapy. In PD-L1 ≥ 50% population, PD-1/L1 had longer OS than chemotherapy (HR 0.71, 0.60-0.84); I + C also had longer OS (HR 0.61, 0.49-0.77) and PFS (HR 0.41,0.34-0.49) than chemotherapy. In indirect analysis (PD-L1 ≥ 50%), I + C was superior to PD-1/L1 in terms of PFS (HR 0.54, 0.35-0.82), but not OS (HR 0.86,. Both treatment-related and immune-mediated adverse events occurred most frequently in the combination therapy group. We suggest that a combination regimen is preferable as first-line treatment for NSCLC patients with different PD-L1 expression, in the meanwhile, in cautious of side effects.

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PD-L1 protein expression in tumour cells and immune cells in mismatch repair protein-deficient and -proficient colorectal cancer: the foundation study using the SP142 antibody and whole section immunohistochemistry

Cited by 22 publications

References 37 publications

The type of distribution of PD-L1 positive immune cells and PD-L1 expression in tumor cells correlate with the development of non-classical differentiation in urinary bladder cancer

The type of distribution of PD-L1 positive immune cells and PD-L1 expression in tumor cells correlate with the development of non-classical differentiation in urinary bladder cancer

PD-L1 expression in colorectal cancer defines three subsets of tumor immune microenvironments

PD‐(L)1 inhibitors vs. chemotherapy vs. their combination in front‐line treatment for NSCLC: An indirect comparison

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