Trained immunity inducers in cancer immunotherapy DOI Creative Commons
Yongjun Sui, Jay A. Berzofsky

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: July 16, 2024

While most of the cancer immunotherapy strategies engage adaptive immunity, especially tumor-associated T cells, small fraction responding patients and types cancers amenable, possibility severe adverse effects limit its usage. More effective general interventions are urgently needed. Recently, a de facto innate immune memory, termed ‘trained immunity’, has become new research focal point, promises to be powerful tool for achieving long-term therapeutic benefits against cancers. Trained immunity-inducing agents such as BCG fungal glucan have been shown able avert suppressive tumor microenvironment (TME), enhance cell responses, eventually lead regression. Here, we review current understating trained immunity induction highlight critical roles emergency granulopoiesis, interferon γ tissue-specific induction. Preclinical clinical studies that exploited inducers summarized, repurposed from other fields proposed. We also outline challenges opportunities in future immunotherapies. envisage more vaccines will combine with therapies.

Language: Английский

Intratumoural administration and tumour tissue targeting of cancer immunotherapies DOI Open Access
Ignacio Melero,

Eduardo Castañón,

Maite Álvarez

et al.

Nature Reviews Clinical Oncology, Journal Year: 2021, Volume and Issue: 18(9), P. 558 - 576

Published: May 18, 2021

Language: Английский

Citations

352

Immune evasion and provocation by Mycobacterium tuberculosis DOI Open Access
Pallavi Chandra, Steven J. Grigsby, Jennifer A. Philips

et al.

Nature Reviews Microbiology, Journal Year: 2022, Volume and Issue: 20(12), P. 750 - 766

Published: July 25, 2022

Language: Английский

Citations

322

NETworking with cancer: The bidirectional interplay between cancer and neutrophil extracellular traps DOI Creative Commons
José M. Adrover, Sheri A. C. McDowell, Xue‐Yan He

et al.

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(3), P. 505 - 526

Published: Feb. 23, 2023

Language: Английский

Citations

146

Innate Immunity and Cancer Pathophysiology DOI Open Access
Laura Maiorino, Juliane Daßler‐Plenker, Lijuan Sun

et al.

Annual Review of Pathology Mechanisms of Disease, Journal Year: 2021, Volume and Issue: 17(1), P. 425 - 457

Published: Nov. 18, 2021

Chronic inflammation increases the risk of several cancers, including gastric, colon, and hepatic cancers. Conversely, tumors, similar to tissue injury, trigger an inflammatory response coordinated by innate immune system. Cellular molecular mediators modulate tumor growth directly influencing adaptive response. Depending on balance cell types signals within microenvironment, can support or restrain tumor. Adding complexity, research from past two decades has revealed that cells are highly heterogeneous plastic, with variable phenotypes depending type, stage, treatment. The field is now cusp being able harness this wealth data (

Language: Английский

Citations

114

100 years of Bacillus Calmette–Guérin immunotherapy: from cattle to COVID-19 DOI Creative Commons
Niyati Lobo, Nathan A. Brooks, Alexandre R. Zlotta

et al.

Nature Reviews Urology, Journal Year: 2021, Volume and Issue: 18(10), P. 611 - 622

Published: June 15, 2021

Bacillus Calmette-Guérin (BCG) is the most widely used vaccine worldwide and has been to prevent tuberculosis for a century. BCG also stimulates an anti-tumour immune response, which urologists have harnessed treatment of non-muscle-invasive bladder cancer. A growing body evidence indicates that offers protection against various non-mycobacterial viral infections. The non-specific effects occur via induction trained immunity form basis hypothesis vaccination could be protect severity coronavirus disease 2019 (COVID-19). This Perspective article highlights key milestones in 100-year history projects its potential role COVID-19 pandemic.

Language: Английский

Citations

113

Fusobacterium nucleatum and cancer DOI Creative Commons
Tamar Alon‐Maimon, Ofer Mandelboim, Gilad Bachrach

et al.

Periodontology 2000, Journal Year: 2022, Volume and Issue: 89(1), P. 166 - 180

Published: March 4, 2022

Abstract Accumulating evidence demonstrates that the oral pathobiont Fusobacterium nucleatum is involved in progression of an increasing number tumors types. Thus far, mechanisms underlying tumor exacerbation by F. include enhancement proliferation, establishment a tumor‐promoting immune environment, induction chemoresistance, and activation checkpoints. This review focuses on mediate tumor‐specific colonization fusobacteria. Elucidating mediating fusobacterial tropism promotion might provide new insights for development novel approaches detection treatment.

Language: Английский

Citations

101

Inducing trained immunity in pro-metastatic macrophages to control tumor metastasis DOI
Chuanlin Ding, Rejeena Shrestha, Xiaojuan Zhu

et al.

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(2), P. 239 - 254

Published: Jan. 5, 2023

Language: Английский

Citations

97

IL-15 Superagonist NAI in BCG-Unresponsive Non–Muscle-Invasive Bladder Cancer DOI Open Access

Karim Chamie,

Sam S. Chang,

Eugene V. Kramolowsky

et al.

NEJM Evidence, Journal Year: 2022, Volume and Issue: 2(1)

Published: Nov. 10, 2022

BackgroundPatients with Bacillus Calmette–Guérin (BCG)–unresponsive non–muscle-invasive bladder cancer (NMIBC) have limited treatment options. The immune cell–activating interleukin-15 (IL-15) superagonist Nogapendekin alfa inbakicept (NAI), also known as N-803, may act synergistically BCG to elicit durable complete responses (CRs) in this patient population.MethodsIn open-label, multicenter study, patients BCG-unresponsive carcinoma situ (CIS) or without Ta/T1 papillary disease were treated intravesical NAI plus (cohort A) alone C). Patients high-grade NMIBC received B). primary end point was the incidence of CR at 3- 6-month assessment visit for cohorts A and C, disease-free survival (DFS) rate 12 months cohort B. Durability, cystectomy avoidance, progression-free survival, disease-specific (DSS), overall secondary points A.ResultsIn A, achieved 58 (71%) 82 (95% confidence interval [CI]=59.6 80.3; median follow-up, 23.9 months), a duration 26.6 CI=9.9 [upper bound not reached]). At 24 CR, Kaplan–Meier estimated probability avoiding DSS 89.2% 100%, respectively. In B (n=72), DFS 55.4% CI=42.0% 66.8%) months, 19.3 CI=7.4 Most treatment-emergent adverse events receiving grade 1 2 (86%); three 3 immune-related occurred.ConclusionsIn novel agent NAI, CRs persistence effect, 100% cancer–specific months. study is ongoing, an target enrollment 200 participants (Funded by ImmunityBio.)

Language: Английский

Citations

74

BCG in Bladder Cancer Immunotherapy DOI Open Access
Song Jiang, Gil Redelman‐Sidi

Cancers, Journal Year: 2022, Volume and Issue: 14(13), P. 3073 - 3073

Published: June 23, 2022

BCG is a live attenuated strain of Mycobacterium bovis that primarily used as vaccine against tuberculosis. In the past four decades, has also been for treatment non-muscle invasive bladder cancer (NMIBC). patients with NMIBC, reduces risk tumor recurrence and decreases likelihood progression to more disease. Despite long-term clinical experience BCG, its mechanism action still being elucidated. Data from animal models human studies suggests activates both innate adaptive arms immune system eventually leading destruction. Herein, we review current data regarding summarize evidence efficacy recommended indications practice.

Language: Английский

Citations

72

The m6A Reader YTHDF2 Promotes Bladder Cancer Progression by Suppressing RIG-I–Mediated Immune Response DOI Creative Commons
Lei Zhang, Yuqing Li, Lingli Zhou

et al.

Cancer Research, Journal Year: 2023, Volume and Issue: 83(11), P. 1834 - 1850

Published: March 20, 2023

Abstract N6-Methyladenosine (m6A) is the most prevalent internal modification of mammalian mRNAs. Recent studies have shown that m6A methyltransferases METTL3 and METTL14 play important roles in urothelial bladder carcinoma (BLCA). To provide a more comprehensive understanding regulatory landscape cancer, we investigated role YTHDF2, crucial reader, BLCA. YTHDF2 was frequently upregulated at both RNA protein level Functionally, promoted proliferation tumor growth BLCA cells vitro vivo, respectively. Integrative sequencing analyses identified RIG-I as downstream target YTHDF2. Mechanistically, bound to coding sequence DDX58 mRNA, which encodes RIG-I, mediated its degradation an m6A-dependent manner. Knockdown inhibited apoptosis cells. Depleting also able reverse effects deficiency. YTHDF2-deficient implanted orthotopically recipient mice activated innate immune response recruitment CD8+ T lymphocytes into bed urothelium. Moreover, deficiency enhanced efficacy Bacillus Calmette-Guérin immunotherapy treatment. This study reveals acts oncogene inhibits facilitate evasion, supporting testing inhibition combination with immunotherapy. Significance: regulates RIG-I–mediated signaling support cancer progression, highlighting functional importance modifications uncovering therapeutic opportunities improve patient outcomes.

Language: Английский

Citations

44