Abnormal expression of Tim‐3 antigen on peripheral blood T cells is associated with progressive disease in osteosarcoma patients

Liu, Hongliang; Zhi, Liqiang; Duan, Ning; Su, Pengxiao

doi:10.1002/2211-5463.12079

Cited by 20 publications

(18 citation statements)

References 28 publications

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“…Evidence suggests that both lymphoid and myeloid lineage activation status in both the local and systemic immune environments may carry clinically useful information regarding osteosarcoma disease progression, metastasis, and survival [16, 17, 46]. However, once the primary tumor is removed, it can no longer provide up-to-date information on the evolving antitumor immune response.…”

Section: Resultsmentioning

confidence: 99%

Using the Spleen as anIn VivoSystemic Immune Barometer Alongside Osteosarcoma Disease Progression and Immunotherapy withα-PD-L1

Markel

Noore

Emery

et al. 2018

Sarcoma

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Indications for immunotherapies are still unclear, and there is a great need for real-time patient immune status monitoring. In this study, we confirmed that the local and systemic immune profiles of an orthotopic osteosarcoma model with or without luciferase transfection were statistically equivalent. Next, we used flow cytometry to describe systemic immune cell populations influenced by osteosarcoma disease progression. When compared to vehicle-inoculated sham mice, it was found that tumor-bearing mice had significant immunophenotype disturbances at approximately 11 weeks after inoculation (at which time 90% of primary tumor-bearing mice have fulminant pulmonary metastases). Percent populations of natural killer cells and T regulatory cells were increased in the spleens of tumor-bearing mice (p < 0.0083) compared to shams. Additionally, T lymphocytes from spleens of tumor-bearing mice showed increased Tim-3/PD-1 exhaustion status (p < 0.0083). There were also increases in the percent populations of myeloid cells and overall M1/M2 macrophage marker expression on tumor-bearing mice spleens versus controls (p < 0.00714). Finally, treatment with 20 μg α-PD-L1 decreased T-cell exhaustion back to sham status, with a corresponding increase in CTLA-4 expression on cytotoxic T cells in the majority of mice tested. Checkpoint inhibition also increased splenic monocyte maturation and returned macrophage M1/M2 marker expression back to sham status. These data suggest that cancer induces systemic immune dysregulation and that these changes may be elucidated and utilized for treatment purposes by sampling the systemic immune environment via the spleen. In addition, treatment with the checkpoint inhibitor α-PD-L1 may neutralize but not overcome the systemic immunological changes induced by a progressing malignancy.

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Section: Resultsmentioning

confidence: 99%

Using the Spleen as anIn VivoSystemic Immune Barometer Alongside Osteosarcoma Disease Progression and Immunotherapy withα-PD-L1

Markel

Noore

Emery

et al. 2018

Sarcoma

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“…In a study by Shang et al (19), TIM-3 expression resulted in tumor cells acquiring features associated with aggressive epithelial-mesenchymal transition and thus may be involved in the pathogenesis of osteosarcoma (19). A recent study revealed that aberrant expression of the TIM-3 antigen on peripheral blood T cells is associated with progressive disease in patients with osteosarcoma, and TIM-3 may be a possible diagnostic biomarker of osteosarcoma and/or a prognostic biomarker of osteosarcoma progression (20).…”

Section: Discussionmentioning

confidence: 99%

TIM‑3 expression and its association with overall survival in primary osteosarcoma

Chen

Zhang

et al. 2019

Oncol Lett

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T-cell immunoglobulin and mucin domaincontaining-3 (TIM-3) performs a critical function in immune tolerance by suppressing the activation and proliferation of T cells. TIM-3 serves an important role in tumor progression in a number of carcinomas, including non-small cell lung cancer, hepatitis B virus-associated hepatocellular carcinoma, Langerhans cell sarcoma, head and neck cancer and follicular B cell non-Hodgkin lymphoma. The aim of the present study was to evaluate the possible association of TIM-3 with the prognosis of osteosarcoma. TIM-3 expression was assessed by immunohistochemical analysis in osteosarcoma tissues. The association between TIM-3 expression and prognosis was examined. To assess the association between TIM-3 expression levels and clinicopathological features, a Fisher's exact test was used. TIM-3 overexpression was indicated to be associated with surgical treatment and survival. Kaplan-Meier analysis indicated that TIM-3 is an independent predictor of overall survival, and its overexpression was indicated to be associated with poor prognosis in patients with osteosarcoma. Additionally, reverse transcription-quantitative polymerase chain reaction and western blot analysis were carried out to evaluate TIM-3 expression levels in fresh tumor tissue samples, adjacent-tissue samples, osteosarcoma cell lines, and in an osteoblastic cell line. TIM-3 was indicated to be overexpressed in fresh osteosarcoma tissue samples and in osteosarcoma cell lines. In conclusion, TIM-3 overexpression is associated with poor survival among patients with osteosarcoma and may be a possible therapeutic target in these types of tumors.

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“…A third inhibitory receptor on T cells, Tim-3, was also analysed given its emerging role as an inhibitor of T cell function and anti-tumour immunity[ 31 ]. Elevated levels of Tim-3 on T cells from osteosarcoma patients have been associated with poor survival while Tim-3 + PD-1 + tumour-specific T cells in melanoma were found to be dysfunctional [ 18 , 32 ]. Blocking antibodies against Tim-3 have been shown to promote anti-tumour immunity both as sole agents and in combination with other treatments and antibodies against additional inhibitory receptors [ 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

Elevated frequencies of CD8 T cells expressing PD-1, CTLA-4 and Tim-3 within tumour from perineural squamous cell carcinoma patients

et al. 2017

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Perineural spread of tumour cells along cranial nerves is a severe complication of primary cutaneous squamous cell carcinomas of the head and neck region. While surgical excision of the tumour is the treatment of choice, removal of all the tumour is often complicated by the neural location and recurrence is frequent. Non-invasive immune treatments such as checkpoint inhibitor blockade may be useful in this set of tumours although little is understood about the immune response to perineural spread of squamous cell carcinomas. Immunohistochemistry studies suggest that perineural tumour contains a lymphocyte infiltrate but it is difficult to quantitate the different proportions of immune cell subsets and expression of checkpoint molecules such as PD-1, Tim-3 and CTLA-4. Using flow cytometry of excised perineural tumour tissue, we show that a T cell infiltrate is prominent in addition to less frequent B cell, NK cell and NKT cell infiltrates. CD8 T cells are more frequent than other T cells in the tumour tissue. Amongst CD8 T cells, the frequency of Tim-3, CTLA-4 and PD-1 expressing cells was significantly greater in the tumour relative to the blood, a pattern that was repeated for Tim-3, CTLA-4 and PD-1 amongst non-CD8 T cells. Using immunohistochemistry, PD-1 and PD-L1-expression could be detected in close proximity amongst perineural tumour tissue. The data suggest that perineural SCC contains a mixture of immune cells with a predominant T cell infiltrate containing CD8 T cells. Elevated frequencies of tumour-associated Tim-3+, CTLA-4+ and PD-1+ CD8 T cells suggests that a subset of patients may benefit from local antibody blockade of these checkpoint inhibitors.

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Abnormal expression of Tim‐3 antigen on peripheral blood T cells is associated with progressive disease in osteosarcoma patients

Cited by 20 publications

References 28 publications

Using the Spleen as anIn VivoSystemic Immune Barometer Alongside Osteosarcoma Disease Progression and Immunotherapy withα-PD-L1

Using the Spleen as anIn VivoSystemic Immune Barometer Alongside Osteosarcoma Disease Progression and Immunotherapy withα-PD-L1

TIM‑3 expression and its association with overall survival in primary osteosarcoma

Elevated frequencies of CD8 T cells expressing PD-1, CTLA-4 and Tim-3 within tumour from perineural squamous cell carcinoma patients

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