High levels of baseline serum IL-10 are associated with reduced clinical benefit from first-line immune checkpoint inhibitor therapy in advanced renal cell carcinoma

Kim, Youngun; Yang, Hannah; Lee, Won Suk; Cheon, Jaekyung; Sang, Yun Beom; Kang, Beodeul; Chon, Hong Jae; Kim, Chan

doi:10.7150/jca.81384

Cited by 5 publications

(3 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, studies have shown that serum IL-10 levels do not correlate with prognosis ( 27 – 29 ). More recently, a relationship between IL-10 and the clinical benefits of immune checkpoint inhibitors has been reported ( 30 , 31 ). The level of serum IL-10 and percentage of CD4 + IL-10 + PBMCs were associated with prognosis and treatment response in patients treated with immune checkpoint inhibitors, respectively.…”

Section: Discussionmentioning

confidence: 99%

Tumor antigen‑specific interleukin‑10‑producing T‑cell response in patients with head and neck squamous cell carcinoma

Horikawa,

Masuda,

Takahashi

et al. 2024

Oncol Lett

View full text Add to dashboard Cite

Interleukin-10 (IL-10) is a highly pleiotropic cytokine that regulates immunological homeostasis through anti-inflammatory and/or immunostimulatory functions. Moreover, IL-10 is well known to exert diverse roles in tumor immunology and immunotherapy. The present study investigated the presence of circulating tumor antigen-specific IL-10-producing T cells in patients with head and neck squamous cell carcinoma (HNSCC), and determined factors that may influence the immunodynamics of IL-10-producing T cells. In vitro , peripheral blood mononuclear cells (PBMCs) stimulated with the tumor antigens p53 and MAGE-A4 were evaluated for interferon (IFN)-γ/IL-10 production using the IFN-γ/IL-10 double-color enzyme-linked immunosorbent spot assay. The proportion of T cells expressing immune checkpoint molecules in PBMCs was analyzed using flow cytometry. Of the 18 patients with HNSCC, 2 (11.1%) and 9 (50.0%) exhibited p53-specific IFN-γ and IL-10 production, respectively. Meanwhile, MAGE-A4-specific IFN-γ and IL-10 production was detected in 4 (28.6%) and 7 (50.0%) of 14 patients. In the p53-specific responses, IL-10-producing T cells were observed in significantly more patients than IFN-γ producing T cells (P=0.0275). In both CD4 + and CD8 + T cells, the proportion of T cells expressing lymphocyte activation gene-3 (Lag-3) was significantly lower in patients with p53-specific IL-10 production than in those without. In certain patients, Lag-3 blockade enhanced tumor antigen-specific IL-10. Taken together, the present study successfully demonstrated that tumor antigen-specific IL-10-producing T cells exist in the peripheral blood of patients with HNSCC and that Lag-3 + T cells may serve an important role in modulating IL-10-producing T cells. These findings provide novel insights into the roles of IL-10 and Lag-3 in mediating antitumor immune responses.

show abstract

Section: Discussionmentioning

confidence: 99%

Tumor antigen‑specific interleukin‑10‑producing T‑cell response in patients with head and neck squamous cell carcinoma

Horikawa,

Masuda,

Takahashi

et al. 2024

Oncol Lett

View full text Add to dashboard Cite

show abstract

“…In general, renal cell TIME is characterized by an overwhelming abundance of immunosuppression which allows cancer cells to evade immune surveillance and cause disease progression. A preponderance of immunosuppressive cytokines such as interleukin-10 (IL-10) and transforming growth factor beta (TGF-b) promotes the differentiation of regulatory T cells (Treg) which in turn inhibit CD8+ T cells from tumor killing (19)(20)(21)(22)(23)(24)(25). In addition, tumor cells may also express PD-L1 which binds with the programmed cell death protein 1 (PD-1) on CD8+ T cells to neutralize its tumoricidal function (10,11).…”

Section: Renal Cancer Immune Environmentmentioning

confidence: 99%

Immunotherapy and stereotactic body radiotherapy for older patients with non-metastatic renal cancer unfit for surgery or decline nephrectomy: practical proposal by the International Geriatric Radiotherapy Group

Nguyen,

Chirila,

Page

et al. 2024

Front. Oncol.

View full text Add to dashboard Cite

The standard of care for non-metastatic renal cancer is surgical resection followed by adjuvant therapy for those at high risk for recurrences. However, for older patients, surgery may not be an option due to the high risk of complications which may result in death. In the past renal cancer was considered to be radio-resistant, and required a higher dose of radiation leading to excessive complications secondary to damage of the normal organs surrounding the cancer. Advances in radiotherapy technique such as stereotactic body radiotherapy (SBRT) has led to the delivery of a tumoricidal dose of radiation with minimal damage to the normal tissue. Excellent local control and survival have been reported for selective patients with small tumors following SBRT. However, for patients with poor prognostic factors such as large tumor size and aggressive histology, there was a higher rate of loco-regional recurrences and distant metastases. Those tumors frequently carry program death ligand 1 (PD-L1) which makes them an ideal target for immunotherapy with check point inhibitors (CPI). Given the synergy between radiotherapy and immunotherapy, we propose an algorithm combining CPI and SBRT for older patients with non-metastatic renal cancer who are not candidates for surgical resection or decline nephrectomy.

show abstract

“…Increased IL-10 expression in primary tumor cells and tumor-associated macrophages has been proposed as a predictor of cancer stage progression and metastatic potential development (87, 173, 174). Moreover, IL-10 circulating levels were found to be elevated in serum of various cancer patients, often accompanied by the increase of other inflammatory markers, and correlated with a poor prognosis (140,(175)(176)(177)(178)(179)(180)(181)(182)(183).…”

Section: Il-10 In Cancermentioning

confidence: 99%

The multifaceted nature of IL-10: regulation, role in immunological homeostasis and its relevance to cancer, COVID-19 and post-COVID conditions

Carlini,

Noonan,

Abdalalem

et al. 2023

Front. Immunol.

109

View full text Add to dashboard Cite

Interleukin-10 (IL-10) is a pleiotropic cytokine that has a fundamental role in modulating inflammation and in maintaining cell homeostasis. It primarily acts as an anti-inflammatory cytokine, protecting the body from an uncontrolled immune response, mostly through the Jak1/Tyk2 and STAT3 signaling pathway. On the other hand, IL-10 can also have immunostimulating functions under certain conditions. Given the pivotal role of IL-10 in immune modulation, this cytokine could have relevant implications in pathologies characterized by hyperinflammatory state, such as cancer, or infectious diseases as in the case of COVID-19 and Post-COVID-19 syndrome. Recent evidence proposed IL-10 as a predictor of severity and mortality for patients with acute or post-acute SARS-CoV-2 infection. In this context, IL-10 can act as an endogenous danger signal, released by tissues undergoing damage in an attempt to protect the organism from harmful hyperinflammation. Pharmacological strategies aimed to potentiate or restore IL-10 immunomodulatory action may represent novel promising avenues to counteract cytokine storm arising from hyperinflammation and effectively mitigate severe complications. Natural bioactive compounds, derived from terrestrial or marine photosynthetic organisms and able to increase IL-10 expression, could represent a useful prevention strategy to curb inflammation through IL-10 elevation and will be discussed here. However, the multifaceted nature of IL-10 has to be taken into account in the attempts to modulate its levels.

show abstract

High levels of baseline serum IL-10 are associated with reduced clinical benefit from first-line immune checkpoint inhibitor therapy in advanced renal cell carcinoma

Cited by 5 publications

References 48 publications

Tumor antigen‑specific interleukin‑10‑producing T‑cell response in patients with head and neck squamous cell carcinoma

Tumor antigen‑specific interleukin‑10‑producing T‑cell response in patients with head and neck squamous cell carcinoma

Immunotherapy and stereotactic body radiotherapy for older patients with non-metastatic renal cancer unfit for surgery or decline nephrectomy: practical proposal by the International Geriatric Radiotherapy Group

The multifaceted nature of IL-10: regulation, role in immunological homeostasis and its relevance to cancer, COVID-19 and post-COVID conditions

Contact Info

Product

Resources

About