Cancer stem cell–immune cell crosstalk in tumour progression

Nature reviews. Cancer, Год журнала: 2021, Номер 21(8), С. 526 - 536

Опубликована: Июнь 8, 2021

Язык: Английский

---

Tumor Mutational Burden as a Predictor of Immunotherapy Response: Is More Always Better?

Clinical Cancer Research, Год журнала: 2020, Номер 27(5), С. 1236 - 1241

Опубликована: Ноя. 16, 2020

Abstract Immune checkpoint inhibitors, including antibodies that block programmed cell death protein-1 (PD-1) and PD-L1, have transformed the management of many cancers. However, majority patients primary or acquired resistance to these immunotherapies. There is a significant unmet need for predictive biomarkers can reliably identify who derive clinically meaningful response from PD-1/PD-L1 blockade. High tumor mutational burden (TMB-H) has shown promise as biomarker in lung cancer, but broad applicability TMB-H across all solid tumors unclear. The FDA approved PD-1 inhibitor, pembrolizumab, therapy with TMB equal greater than 10 mutations/megabase measured by FoundationOne CDx assay. This approval was based on an exploratory analysis KEYNOTE-158 study, which single-arm, phase II multi-cohort study pembrolizumab select, previously treated advanced tumors. Here, we elucidate caveats using universal threshold While recognize importance this other pan-cancer approvals, several questions about remain unanswered. In perspective, discuss clinical trial evidence area. We review relationship between immune microenvironment. highlight risks extrapolating limited number histologies tumors, propose avenues future research.

Язык: Английский

---

A single-cell atlas of the multicellular ecosystem of primary and metastatic hepatocellular carcinoma

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Авг. 6, 2022

Abstract Hepatocellular carcinoma (HCC) represents a paradigm of the relation between tumor microenvironment (TME) and development. Here, we generate single-cell atlas multicellular ecosystem HCC from four tissue sites. We show enrichment central memory T cells (T CM ) in early tertiary lymphoid structures (E-TLSs) assess relationships chronic HBV/HCV infection cell infiltration exhaustion. find MMP9 + macrophages to be terminally differentiated tumor-associated (TAMs) PPARγ pivotal transcription factor driving their differentiation. also characterize heterogeneous subpopulations malignant hepatocytes multifaceted functions shaping immune HCC. Finally, identify seven microenvironment-based subtypes that can predict prognosis patients. Collectively, this large-scale deepens our understanding microenvironment, which might facilitate development new therapy strategies for malignancy.

Язык: Английский

---

Relevance of immune cell and tumor microenvironment imaging in the new era of immunotherapy

Journal of Experimental & Clinical Cancer Research, Год журнала: 2020, Номер 39(1)

Опубликована: Май 18, 2020

Tumor-infiltrating immune cells play a key role against cancer. However, malignant are able to evade the response and establish very complex balance in which different subtypes may drive tumor progression, metastatization resistance therapy. New immunotherapeutic approaches aim at restoring natural increase cancer by mechanisms. The complexity of these interactions heterogeneity cell subpopulations real challenge when trying develop new immunotherapeutics evaluate or predict their efficacy vivo. To this purpose, molecular imaging can offer non-invasive diagnostic tools like radiopharmaceuticals, contrast agents fluorescent dyes. These be useful for preclinical clinical purposes overcome [

Язык: Английский

---

Cancer Stemness Meets Immunity: From Mechanism to Therapy

Cell Reports, Год журнала: 2021, Номер 34(1), С. 108597 - 108597

Опубликована: Янв. 1, 2021

Cancer stem cells (CSCs) are self-renewing that facilitate tumor initiation, promote metastasis, and enhance cancer therapy resistance. Transcriptomic analyses across many types have revealed a prominent association between stemness immune signatures, potentially implying biological interaction such hallmark features of cancer. Emerging experimental evidence has substantiated the influence CSCs on cells, including tumor-associated macrophages, myeloid-derived suppressor T in microenvironment and, reciprocally, importance sustaining CSC its survival niche. This review covers cellular molecular mechanisms underlying symbiotic interactions how heterotypic signaling maintains tumor-promoting ecosystem informs therapeutic strategies intercepting this co-dependency.

Язык: Английский

---

Integrated analysis of single-cell and bulk RNA sequencing data reveals a pan-cancer stemness signature predicting immunotherapy response

Genome Medicine, Год журнала: 2022, Номер 14(1)

Опубликована: Апрель 29, 2022

Although immune checkpoint inhibitor (ICI) is regarded as a breakthrough in cancer therapy, only limited fraction of patients benefit from it. Cancer stemness can be the potential culprit ICI resistance, but direct clinical evidence lacking.

Язык: Английский

---

Circadian Regulator CLOCK Recruits Immune-Suppressive Microglia into the GBM Tumor Microenvironment

Cancer Discovery, Год журнала: 2020, Номер 10(3), С. 371 - 381

Опубликована: Янв. 9, 2020

Glioblastoma (GBM) is a lethal brain tumor containing subpopulation of glioma stem cells (GSC). Pan-cancer analyses have revealed that stemness cancer correlates positively with immunosuppressive pathways in many solid tumors, including GBM, prompting us to conduct gain-of-function screen epigenetic regulators may influence GSC self-renewal and immunity. The circadian regulator CLOCK emerged as top hit enhancing stem-cell self-renewal, which was amplified about 5% human GBM cases. its heterodimeric partner BMAL1 enhanced triggered protumor immunity via transcriptional upregulation OLFML3, novel chemokine recruiting immune-suppressive microglia into the microenvironment. In models, or OLFML3 depletion reduced intratumoral density extended overall survival. We conclude CLOCK-BMAL1 complex contributes key hallmarks maintenance immunosuppression and, together downstream target represents new therapeutic targets for this disease. SIGNIFICANCE: Circadian drives metabolism promotes infiltration through direct regulation microglia-attracting chemokine, OLFML3. and/or represent GBM.This article highlighted This Issue feature, p. 327.

Язык: Английский

---

Mechanisms of acquired tumor drug resistance

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2019, Номер 1872(2), С. 188310 - 188310

Опубликована: Авг. 20, 2019

Язык: Английский

---

Tumor microenvironment heterogeneity an important mediator of prostate cancer progression and therapeutic resistance

npj Precision Oncology, Год журнала: 2022, Номер 6(1)

Опубликована: Май 4, 2022

Prostate cancer is characterized by a high degree of heterogeneity, which poses major challenge to precision therapy and drug development. In this review, we discuss how nongenetic factors contribute heterogeneity prostate cancer. We also tumor phenotypic switching related anticancer therapies. Lastly, summarize the challenges targeting environments, emphasize that continued exploration needed in order offer personalized for advanced patients.

Язык: Английский

---

How cancer cells make and respond to interferon-I

Trends in cancer, Год журнала: 2022, Номер 9(1), С. 83 - 92

Опубликована: Окт. 8, 2022

Acute exposure of cancer cells to high concentrations type I interferon (IFN-I) drives growth arrest and apoptosis, whereas chronic low provides important prosurvival advantages. Tyrosine-phosphorylated IFN-stimulated gene (ISG) factor 3 (ISGF3) acute deleterious responses IFN-I, unphosphorylated (U-)ISGF3, lacking tyrosine phosphorylation, essential constitutive mechanisms. Surprisingly, programmed cell death-ligand 1 (PD-L1), often expressed on the surfaces tumor well recognized for its importance in inactivating cytotoxic T cells, also has cell-intrinsic protumor activities, including dampening levels IFN-I sustaining expression that benefit tumors. More thorough understanding newly complex roles may lead identification novel therapeutic strategies.

Язык: Английский

---