Robust anti-tumor immunity and memory in Rag-1-deficient mice following adoptive transfer of cytokine-primed splenocytes and tumor CD80 expression

Ganesan, P; Alexander, Stephen I.; Watson, Debbie; Logan, Grant J; Zhang, Geoff Y.; Alexander, Ian E.

doi:10.1007/s00262-007-0339-7

Cited by 4 publications

(4 citation statements)

References 40 publications

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“…For instance, NK1.1 + cells lost the anti-tumorigenic function in mice bearing TC-1/dCD80-1-compared with those with TC-1-induced tumors. Our data correspond to the observation of an NK cell-mediated reduction of CD80 high tumor growth [5]. Surprisingly, we observed that CD80 deactivation in tumor cells markedly enhanced infiltration by NK and NKT cells, although the depletion of NK1.1 + cells did not affect TC-1/dCD80-1-induced tumor growth.…”

Section: Discussionsupporting

confidence: 90%

“…However, CTLA-4 is mainly expressed on activated T cells, while CD28 is expressed on T cells constitutively [3]. It has been previously reported that the expression level of CD80 may regulate the pro-/anti-oncogenic role of CD80 on tumor cells [4][5][6]. Low levels of CD80 expression serve as a mechanism of tumor escape from immune surveillance due to a higher affinity and, therefore, preferential binding of CTLA-4 to CD80 compared with that for CD28.…”

Section: Introductionmentioning

confidence: 99%

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CD80 Expression on Tumor Cells Alters Tumor Microenvironment and Efficacy of Cancer Immunotherapy by CTLA-4 Blockade

Vackova

Poláková

Johari

et al. 2021

Cancers

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Cluster of differentiation (CD) 80 is mainly expressed in immune cells but can also be found in several types of cancer cells. This molecule may either activate or inhibit immune reactions. Here, we determined the immunosuppressive role of CD80 in the tumor microenvironment by CRISPR/Cas9-mediated deactivation of the corresponding gene in the mouse oncogenic TC-1 cell line. The tumor cells with deactivated CD80 (TC-1/dCD80-1) were more immunogenic than parental cells and induced tumors that gained sensitivity to cytotoxic T-lymphocyte antigen 4 (CTLA-4) blockade, as compared with the TC-1 cells. In vivo depletion experiments showed that the deactivation of CD80 switched the pro-tumorigenic effect of macrophages observed in TC-1-induced tumors into an anti-tumorigenic effect in TC-1/dCD80-1 tumors and induced the pro-tumorigenic activity of CD4+ cells. Moreover, the frequency of lymphoid and myeloid cells and the CTLA-4 expression by T helper (Th)17 cells were increased in TC-1/dCD80-1- compared with that in the TC-1-induced tumors. CTLA-4 blockade downregulated the frequencies of most immune cell types and upregulated the frequency of M2 macrophages in the TC-1 tumors, while it increased the frequency of lymphoid cells in TC-1/dCD80-1-induced tumors. Furthermore, the anti-CTLA-4 therapy enhanced the frequency of CD8+ T cells as well as CD4+ T cells, especially for a Th1 subset. Regulatory T cells (Treg) formed the most abundant CD4+ T cell subset in untreated tumors. The anti-CTLA-4 treatment downregulated the frequency of Treg cells with limited immunosuppressive potential in the TC-1 tumors, whereas it enriched this type of Treg cells and decreased the Treg cells with high immunosuppressive potential in TC-1/dCD80-1-induced tumors. The immunosuppressive role of tumor-cell-expressed CD80 should be considered in research into biomarkers for the prediction of cancer patients’ sensitivity to immune checkpoint inhibitors and for the development of a tumor-cell-specific CD80 blockade.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

CD80 Expression on Tumor Cells Alters Tumor Microenvironment and Efficacy of Cancer Immunotherapy by CTLA-4 Blockade

Vackova

Poláková

Johari

et al. 2021

Cancers

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“…IL-21 may be a promising candidate for cancer immunotherapy as it has pleiotropic roles in immune cells, yet does not support Treg function. A combination of IL-15 and IL-21 may be a choice for future therapeutic regimens, as suggested by some mouse studies (Ganesan et al 2007;Margalit et al 2005). Though the combinations of above therapies eYciently reduce bulky tumor mass, however, these therapies are less eVective in eliminating residual tumors and in preventing disease recurrence.…”

Section: Optimization Of Bcg Immunotherapy From the Insight Of Cytokimentioning

confidence: 97%

BCG response prediction with cytokine gene variants and bladder cancer: where we are?

Ahirwar

Manchanda

Mittal

et al. 2011

J Cancer Res Clin Oncol

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“…The affinity of CTLA-4 to CD80 is approximately ten times greater than its affinity to CD28. Also, CTLA-4 is predominantly expressed on T cells that have been activated, whereas CD28 is expressed on T cells in a constitutive manner (94). Prior studies have indicated that the expression level of CD80 might influence the pro-/anti-oncogenic function of CD80 on neoplastic cells (93-97).…”

Section: Cd80mentioning

confidence: 99%

Aging-related biomarker discovery in the era of immune checkpoint inhibitors for cancer patients

Al-Danakh,

Safi,

Jian

et al. 2024

Front. Immunol.

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Older patients with cancer, particularly those over 75 years of age, often experience poorer clinical outcomes compared to younger patients. This can be attributed to age-related comorbidities, weakened immune function, and reduced tolerance to treatment-related adverse effects. In the immune checkpoint inhibitors (ICI) era, age has emerged as an influential factor impacting the discovery of predictive biomarkers for ICI treatment. These age-linked changes in the immune system can influence the composition and functionality of tumor-infiltrating immune cells (TIICs) that play a crucial role in the cancer response. Older patients may have lower levels of TIICs infiltration due to age-related immune senescence particularly T cell function, which can limit the effectivity of cancer immunotherapies. Furthermore, age-related immune dysregulation increases the exhaustion of immune cells, characterized by the dysregulation of ICI-related biomarkers and a dampened response to ICI. Our review aims to provide a comprehensive understanding of the mechanisms that contribute to the impact of age on ICI-related biomarkers and ICI response. Understanding these mechanisms will facilitate the development of treatment approaches tailored to elderly individuals with cancer.

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Robust anti-tumor immunity and memory in Rag-1-deficient mice following adoptive transfer of cytokine-primed splenocytes and tumor CD80 expression

Cited by 4 publications

References 40 publications

CD80 Expression on Tumor Cells Alters Tumor Microenvironment and Efficacy of Cancer Immunotherapy by CTLA-4 Blockade

CD80 Expression on Tumor Cells Alters Tumor Microenvironment and Efficacy of Cancer Immunotherapy by CTLA-4 Blockade

BCG response prediction with cytokine gene variants and bladder cancer: where we are?

Aging-related biomarker discovery in the era of immune checkpoint inhibitors for cancer patients

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