Synergizing radiotherapy and immunotherapy: Current challenges and strategies for optimization

Rajeev‐Kumar, Greeshma; Pitroda, Sean P.

doi:10.1016/j.neo.2022.100867

Cited by 15 publications

(7 citation statements)

References 65 publications

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“…CEACAM1 is an inhibitory ligand expressed on cancer cells that can impair T cell function through either homophilic interactions or interactions with TIM3 [55][56][57][58] . In addition to PDL1, our study suggests that CEACAM1 may also be a promising immunotherapeutic target, particularly for HDR deficient cancers, and may lead to more efficacious combination with radiation treatment than has been seen in prior immunotherapy and radiation trials [59][60][61][62]…”

Section: Discussionmentioning

confidence: 83%

Genome scale CRISPR screens identify actin capping proteins as key modulators of therapeutic responses to radiation and immunotherapy

Verma,

Renauer,

Dong

et al. 2024

Preprint

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Radiotherapy (RT), is a fundamental treatment for malignant tumors and is used in over half of cancer patients. As radiation can promote anti-tumor immune effects, a promising therapeutic strategy is to combine radiation with immune checkpoint inhibitors (ICIs). However, the genetic determinants that impact therapeutic response in the context of combination therapy with radiation and ICI have not been systematically investigated. To unbiasedly identify the tumor intrinsic genetic factors governing such responses, we perform a set of genome-scale CRISPR screens in melanoma cells for cancer survival in response to low-dose genotoxic radiation treatment, in the context of CD8 T cell co-culture and with anti-PD1 checkpoint blockade antibody. Two actin capping proteins, Capza3 and Capg, emerge as top hits that upon inactivation promote the survival of melanoma cells in such settings. Capza3 and Capg knockouts (KOs) in mouse and human cancer cells display persistent DNA damage due to impaired homology directed repair (HDR); along with increased radiation, chemotherapy, and DNA repair inhibitor sensitivity. However, when cancer cells with these genes inactivated were exposed to sublethal radiation, inactivation of such actin capping protein promotes activation of the STING pathway, induction of inhibitory CEACAM1 ligand expression and resistance to CD8 T cell killing. Patient cancer genomics analysis reveals an increased mutational burden in patients with inactivating mutations in CAPG and/or CAPZA3, at levels comparable to other HDR associated genes. There is also a positive correlation between CAPG expression and activation of immune related pathways and CD8 T cell tumor infiltration. Our results unveil the critical roles of actin binding proteins for efficient HDR within cancer cells and demonstrate a previously unrecognized regulatory mechanism of therapeutic response to radiation and immunotherapy.

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Section: Discussionmentioning

confidence: 83%

Genome scale CRISPR screens identify actin capping proteins as key modulators of therapeutic responses to radiation and immunotherapy

Verma,

Renauer,

Dong

et al. 2024

Preprint

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“…Appropriate RT can also induce ICD of tumor cells, release related antigens, improve the microenvironment to attract immune cell infiltration, and increase the immunosensitivity of tumor cells. [ 85 ] However, RT typically has low immunogenicity, and high‐dose radiotherapy may inhibit the immune system. Combining immunotherapy with radiotherapy can enhance the immunogenicity of radiotherapy, activate antitumor immune circulation, and inhibit distal metastasis.…”

Section: Physical Therapy Combined With Immunotherapymentioning

confidence: 99%

Nanotechnology‐Empowered Combination Cancer Immunotherapies: Mechanisms, Synergies, and Perspectives

Pan,

Xue,

Liang

2024

Advanced NanoBiomed Research

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This review is aiming to systematically elucidate the unique role of nanotechnology in optimizing therapeutic modalities for combinatorial cancer immunotherapy, which enables the synergistic integration of multiple treatment strategies. In particular, nanotechnology has enabled the synergistic combination of immunotherapy with physical therapies, chemotherapy, metal therapy, and nucleic acid therapy. In each combination regimen, nanocarriers play multifaceted roles by achieving targeted codelivery of different therapeutics and optimizing each individual treatment modality. This offers new paradigms to guide precision medicine in cancer treatment. Immunotherapy alone is unlikely to achieve personalized precision medicine for cancer, and new treatment modalities are needed in the future. To overcome technical bottlenecks and realize precise regulation of the tumor microenvironment for personalized cancer treatment, it is crucial to develop novel nanosystems with integrated sensing, targeting, and therapeutic functionalities.

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“…However, careful management of the timing, sequencing, and dosing of both approaches is necessary to achieve the best therapeutic results while minimizing adverse effects. In this way, several clinical trials are ongoing [196]. Along with radiotherapy, PRRT can also play a crucial role in combination therapies.…”

Section: Combination Of Prrt With Immunotherapiesmentioning

confidence: 99%

Recent Pre-Clinical Advancements in Nuclear Medicine: Pioneering the Path to a Limitless Future

Echavidre,

Fagret,

Faraggi

et al. 2023

Cancers

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The theranostic approach in oncology holds significant importance in personalized medicine and stands as an exciting field of molecular medicine. Significant achievements have been made in this field in recent decades, particularly in treating neuroendocrine tumors using 177-Lu-radiolabeled somatostatin analogs and, more recently, in addressing prostate cancer through prostate-specific-membrane-antigen targeted radionuclide therapy. The promising clinical results obtained in these indications paved the way for the further development of this approach. With the continuous discovery of new molecular players in tumorigenesis, the development of novel radiopharmaceuticals, and the potential combination of theranostics agents with immunotherapy, nuclear medicine is poised for significant advancements. The strategy of theranostics in oncology can be categorized into (1) repurposing nuclear medicine agents for other indications, (2) improving existing radiopharmaceuticals, and (3) developing new theranostics agents for tumor-specific antigens. In this review, we provide an overview of theranostic development and shed light on its potential integration into combined treatment strategies.

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Synergizing radiotherapy and immunotherapy: Current challenges and strategies for optimization

Cited by 15 publications

References 65 publications

Genome scale CRISPR screens identify actin capping proteins as key modulators of therapeutic responses to radiation and immunotherapy

Genome scale CRISPR screens identify actin capping proteins as key modulators of therapeutic responses to radiation and immunotherapy

Nanotechnology‐Empowered Combination Cancer Immunotherapies: Mechanisms, Synergies, and Perspectives

Recent Pre-Clinical Advancements in Nuclear Medicine: Pioneering the Path to a Limitless Future

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