The Immune Profile of Pituitary Adenomas and a Novel Immune Classification for Predicting Immunotherapy Responsiveness

Wang, Zihao; Guo, Xiaopeng; Gao, Lu; Deng, Kan; Lian, Wei; Bao, Xinjie; Feng, Ming; Duan, Lian; Zhu, Huijuan; Xing, Bing

doi:10.1210/clinem/dgaa449

Cited by 34 publications

(26 citation statements)

References 64 publications

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“…It has been demonstrated that tumor invasion is highly associated with the immune TME in PA 22 . Thus, we explored the infiltration characteristics of the immune cells in PAs through IHC staining.…”

Section: Resultsmentioning

confidence: 99%

Lactate-induced M2 polarization of tumor-associated macrophages promotes the invasion of pituitary adenoma by secreting CCL17

Zhang¹,

Xu²,

Xu³

et al. 2021

Theranostics

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Background: Lactate greatly contributes to the regulation of intracellular communication within the tumor microenvironment (TME). However, the role of lactate in pituitary adenoma (PA) invasion is unclear. In this study, we aimed to clarify the effects of lactate on the TME and the effects of TME on PA invasion. Methods: To explore the correlation between TME acidosis and tumor invasion, LDHA and LAMP2 expression levels were quantified in invasive (n = 32) and noninvasive (n = 32) PA samples. The correlation between immune cell infiltration and tumor invasion was evaluated in 64 PAs. Critical chemokine and key signaling pathway components were detected by qPCR, Western blotting, siRNA knockdown, and specific inhibitors. The functional consequences of CCR4 signaling inhibition were evaluated in vitro and in vivo . Results: Lactate was positively associated with PA invasion. Of the 64 PA tissues, invasive PAs were related to high infiltration of M2-like tumor-associated macrophages (TAMs) (P < 0.05). Moreover, lactate secreted from PA cells facilitated M2 polarization via the mTORC2 and ERK signaling pathways, while activated TAMs secreted CCL17 to promote PA invasion via the CCL17/CCR4/mTORC1 axis. According to univariate analysis of clinical data, high CCL17 expression was associated with larger tumor size (P = 0.0438), greater invasion (P = 0.0334), and higher susceptibility to postoperative recurrence (P = 0.0195) in human PAs. Conclusion: This study illustrates the dynamics between PA cells and immune TME in promoting PA invasion via M2 polarization. CCL17 levels in the TME are related to the PA invasiveness and clinical prognosis, and the CCL17/CCR4/mTOCR1 axis may serve as potential therapeutic targets for Pas.

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Section: Resultsmentioning

confidence: 99%

Lactate-induced M2 polarization of tumor-associated macrophages promotes the invasion of pituitary adenoma by secreting CCL17

Zhang¹,

Xu²,

Xu³

et al. 2021

Theranostics

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“…Ipilimumab (IPI) is a checkpoint inhibitor that inhibits the action of Cytotoxic T-lymphocyteassociated protein 4 (CTLA-4), which downregulates immune response (82). CTLA-4 and PD-1 are both expressed in pituitary adenomas (83)(84)(85). This is thought to be a mechanism by which immunotherapy can contribute to the treatment of pituitary tumors.…”

Section: Immunotherapymentioning

confidence: 99%

Multimodal Non-Surgical Treatments of Aggressive Pituitary Tumors

et al. 2021

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Up to 35% of aggressive pituitary tumors recur and significantly affect mortality and quality of life. Management can be challenging and often requires multimodal treatment. Current treatment options, including surgery, conventional medical therapies such as dopamine agonists, somatostatin receptor agonists and radiotherapy, often fail to inhibit pituitary tumor growth. Recently, anti-tumor effects of chemotherapeutic drugs such as Temozolomide, Capecitabine, and Everolimus, as well as peptide receptor radionuclide therapy on aggressive pituitary tumors have been increasingly investigated and yield mixed, although sometimes promising, outcomes. The purpose of this review is to provide thorough information on non-surgical medical therapies and their efficacies and used protocols for aggressive pituitary adenomas from pre-clinical level to clinical use.

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“…Research conducted by Wang et al showed that there is a different distribution of tumor-infiltration immune cells (TIICs) between PAs and the normal pituitary gland, and there are also differences among different PA subtypes. In addition, three immune clusters can be identified among PAs according to their distribution, and each one of PAs shows unique characteristics [ 38 ]. PAs can be classified into functional pituitary adenomas (FPAs) and non-functional pituitary adenomas (NFPAs) according to the hormone secretion [ 39 ].…”

Section: Immune Cells Infiltrate In Pasmentioning

confidence: 99%

Research advances on the immune research and prospect of immunotherapy in pituitary adenomas

Nie

Fang

et al. 2021

World J Surg Onc

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Background Pituitary adenomas are one type of intracranial tumor, which can be divided into microadenoma (≤ 1 cm), macroadenoma (> 1 cm), and giant adenoma (≥ 4 cm) according to their diametral sizes. They are benign, typically slow-progressing, whereas the biological behavior of some of them is invasive, which presents a major clinical challenge. Treatment of some pituitary adenomas is still difficult due to drug resistance or multiple relapses, usually after surgery, medication, and radiation. At present, no clear prediction and treatment biomarkers have been found in pituitary adenomas and some of them do not cause clinical symptoms, so patients are often found to be ill through physical examination, and some are even found through autopsy. With the development of research on pituitary adenomas, the immune response has become a hot spot and may serve as a novel disease marker and therapeutic target. The distribution and function of immune cells and their secreted molecules in pituitary adenomas are extremely complex. Researchers found that infiltration of immune cells may have a positive effect on the treatment and prognosis of pituitary adenomas. In this review, we summarized the advance of tumor immunity in pituitary adenomas, revealing the immunity molecules as potential biomarkers as well as therapeutic agents for pituitary adenomas. Conclusion The immune studies related to pituitary adenomas may help us find relevant immune markers. At the same time, the exploration of immunotherapy also provides new options for the treatment of pituitary adenomas.

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The Immune Profile of Pituitary Adenomas and a Novel Immune Classification for Predicting Immunotherapy Responsiveness

Abstract: Abstract Context The tumor immune microenvironment is associated with clinical outcomes and immunotherapy responsiveness. Objective To investigate the intratumoral immune profile of pituitary adenomas (PAs) and its clinical relevance and to explore a novel immune … Show more

Cited by 34 publications

References 64 publications

Lactate-induced M2 polarization of tumor-associated macrophages promotes the invasion of pituitary adenoma by secreting CCL17

Lactate-induced M2 polarization of tumor-associated macrophages promotes the invasion of pituitary adenoma by secreting CCL17

Multimodal Non-Surgical Treatments of Aggressive Pituitary Tumors

Research advances on the immune research and prospect of immunotherapy in pituitary adenomas

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