Modulating cancer mechanopathology to restore vascular function and enhance immunotherapy DOI Creative Commons
Fotios Mpekris, Myrofora Panagi, Antonia Charalambous

et al.

Cell Reports Medicine, Journal Year: 2024, Volume and Issue: 5(7), P. 101626 - 101626

Published: June 28, 2024

Solid tumor pathology, characterized by abnormalities in the microenvironment (TME), challenges therapeutic effectiveness. Mechanical factors, including increased stiffness and accumulation of intratumoral forces, can determine success cancer treatments, defining tumor's "mechanopathology" profile. These cause extensive vascular compression, leading to hypoperfusion hypoxia. Hypoperfusion hinders drug delivery, while hypoxia creates an unfavorable TME, promoting progression through immunosuppression, heightened metastatic potential, resistance, chaotic angiogenesis. Strategies targeting TME mechanopathology, such as stroma normalization, hold promise enhancing therapies with some already advancing clinic. Normalization be achieved using anti-angiogenic agents, mechanotherapeutics, immune checkpoint inhibitors, engineered bacterial therapeutics, metronomic nanomedicine, ultrasound sonopermeation. Here, we review methods developed rectify which have even led cures preclinical models, discuss their bench-to-bedside translation, derivation biomarkers from mechanopathology for personalized therapy.

Language: Английский

Immune escape of head and neck cancer mediated by the impaired MHC-I antigen presentation pathway DOI
Xiaobo Luo, Yan Qiu, Zackary R. Fitzsimonds

et al.

Oncogene, Journal Year: 2024, Volume and Issue: 43(6), P. 388 - 394

Published: Jan. 4, 2024

Language: Английский

Citations

11
Epigenetic modulation of antitumor immunity and immunotherapy response in breast cancer: biological mechanisms and clinical implications DOI Creative Commons
Jun Yin, Tiezheng Gu, Norin Chaudhry

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 10, 2024

Breast cancer (BC) is the most common non-skin and second leading cause of death in American women. The initiation progression BC can proceed through accumulation genetic epigenetic changes that allow transformed cells to escape normal cell cycle checkpoint control. Unlike nucleotide mutations, such as DNA methylation, histone posttranslational modifications (PTMs), nucleosome remodeling non-coding RNAs are generally reversible therefore potentially responsive pharmacological intervention. Epigenetic dysregulations critical mechanisms for impaired antitumor immunity, evasion immune surveillance, resistance immunotherapy. Compared highly immunogenic tumor types, melanoma or lung cancer, breast has been viewed an immunologically quiescent which displays a relatively low population tumor-infiltrating lymphocytes (TIL), mutational burden (TMB) modest response rates inhibitors (ICI). Emerging evidence suggests agents targeting aberrant modifiers may augment host immunity via several interrelated enhancing antigen presentation, activation cytotoxic T cells, inhibition immunosuppressive boosting ICI, induction (ICD). These discoveries have established promising basis using combinatorial approaches drugs with immunotherapy innovative paradigm improve outcomes patients. In this review, we summarize current understanding how processes regulate function immunogenicity context microenvironment. Moreover, discuss therapeutic potential latest clinical trials combination blockers cancer.

Language: Английский

Citations

11
Understanding and overcoming resistance to immunotherapy in genitourinary cancers DOI Creative Commons

S. Evans,

Yash Jani,

Caroline S. Jansen

et al.

Cancer Biology & Therapy, Journal Year: 2024, Volume and Issue: 25(1)

Published: April 17, 2024

The introduction of novel immunotherapies has significantly transformed the treatment landscape genitourinary (GU) cancers, even becoming standard care in some settings. One such type immunotherapy, immune checkpoint inhibitors (ICIs) like nivolumab, ipilimumab, pembrolizumab, and atezolizumab play a pivotal role by disturbing signaling pathways that limit system's ability to fight tumor cells. Despite profound impact these treatments, not all tumors are responsive. Recent research efforts have been focused on understanding how cancer cells manage evade response identifying possible mechanisms behind resistance immunotherapy. In response, ICIs being combined with other treatments reduce attack through multiple cellular pathways. Additionally, novel, targeted strategies currently investigated develop innovative methods overcoming failure. This article presents comprehensive overview immunotherapy GU cancers as described literature. It explores studies identified genetic markers, cytokines, proteins may predict or we review current overcome this resistance, which include combination sequential therapies, insights into host profile, new therapies. Various approaches combine chemotherapy, therapy, vaccines, radiation studied an effort more effectively While each therapies shown efficacy clinical trials, deeper underscores potential particularly promising area research. Currently, several agents development, along identification key mediators involved resistance. Further is necessary identify predictors response.

Language: Английский

Citations

11
Current Landscape of Cancer Immunotherapy: Harnessing the Immune Arsenal to Overcome Immune Evasion DOI Creative Commons
Ankita Mitra, Anoop Kumar, Nitin Amdare

et al.

Biology, Journal Year: 2024, Volume and Issue: 13(5), P. 307 - 307

Published: April 28, 2024

Cancer immune evasion represents a leading hallmark of cancer, posing significant obstacle to the development successful anticancer therapies. However, landscape cancer treatment has significantly evolved, transitioning into era immunotherapy from conventional methods such as surgical resection, radiotherapy, chemotherapy, and targeted drug therapy. Immunotherapy emerged pivotal component in treatment, harnessing body’s system combat offering improved prognostic outcomes for numerous patients. The remarkable success spurred efforts enhance clinical efficacy existing agents strategies. Several immunotherapeutic approaches have received approval treatments, while others are currently preclinical trials. This review explores recent progress unraveling mechanisms evaluates effectiveness diverse strategies, including vaccines, adoptive cell therapy, antibody-based treatments. It encompasses both established treatments those under investigation, providing comprehensive overview through immunological approaches. Additionally, article emphasizes current developments, limitations, challenges immunotherapy. Furthermore, by integrating analyses resistance exploring combination strategies personalized approaches, it offers valuable insights crucial novel

Language: Английский

Citations

11
Modulating cancer mechanopathology to restore vascular function and enhance immunotherapy DOI Creative Commons
Fotios Mpekris, Myrofora Panagi, Antonia Charalambous

et al.

Cell Reports Medicine, Journal Year: 2024, Volume and Issue: 5(7), P. 101626 - 101626

Published: June 28, 2024

Solid tumor pathology, characterized by abnormalities in the microenvironment (TME), challenges therapeutic effectiveness. Mechanical factors, including increased stiffness and accumulation of intratumoral forces, can determine success cancer treatments, defining tumor's "mechanopathology" profile. These cause extensive vascular compression, leading to hypoperfusion hypoxia. Hypoperfusion hinders drug delivery, while hypoxia creates an unfavorable TME, promoting progression through immunosuppression, heightened metastatic potential, resistance, chaotic angiogenesis. Strategies targeting TME mechanopathology, such as stroma normalization, hold promise enhancing therapies with some already advancing clinic. Normalization be achieved using anti-angiogenic agents, mechanotherapeutics, immune checkpoint inhibitors, engineered bacterial therapeutics, metronomic nanomedicine, ultrasound sonopermeation. Here, we review methods developed rectify which have even led cures preclinical models, discuss their bench-to-bedside translation, derivation biomarkers from mechanopathology for personalized therapy.

Language: Английский

Citations

10