Overcoming Immune Resistance With Radiation Therapy in Prostate Cancer

Mulvey, Arthur; Muggeo-Bertin, Emilien; Berthold, Dominik R.; Herrera, Fernanda G.

doi:10.3389/fimmu.2022.859785

Cited by 7 publications

(2 citation statements)

References 168 publications

(234 reference statements)

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“…In bladder and kidney cancer, immunotherapy has emerged as the first-line treatment (Lenis et al, 2020;Rizzo et al, 2022). However, PCa, characterized as a "cold tumor", has often been regarded as an "immune desert" (Mulvey et al, 2022), with only 2%-3% of patients showing sensitivity to immunotherapy (Cornford et al, 2021). HNRNPA2B1 and METTL3, key regulators of m6A modification, play a significant role in immune regulation within the tumor microenvironment.…”

Section: Rna Modifications In the Tumor Microenvironment Of Pcamentioning

confidence: 99%

The functions and mechanisms of RNA modification in prostate: Current status and future perspectives

Zhang,

Liu,

et al. 2024

Front. Genet.

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The increasing incidence and mortality of prostate cancer worldwide significantly impact the life span of male patients, emphasizing the urgency of understanding its pathogenic mechanism and associated molecular changes that regulate tumor progression for effective prevention and treatment. RNA modification, an important post-transcriptional regulatory process, profoundly influences tumor cell growth and metabolism, shaping cell fate. Over 170 RNA modification methods are known, with prominent research focusing on N6-methyladenosine, N7-methylguanosine, N1-methyladenosine, 5-methylcytidine, pseudouridine, and N4-acetylcytidine modifications. These alterations intricately regulate coding and non-coding RNA post-transcriptionally, affecting the stability of RNA and protein expression levels. This article delves into the latest advancements and challenges associated with various RNA modifications in prostate cancer tumor cells, tumor microenvironment, and core signaling molecule androgen receptors. It aims to provide new research targets and avenues for molecular diagnosis, treatment strategies, and improvement of the prognosis in prostate cancer.

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Section: Rna Modifications In the Tumor Microenvironment Of Pcamentioning

confidence: 99%

The functions and mechanisms of RNA modification in prostate: Current status and future perspectives

Zhang,

Liu,

et al. 2024

Front. Genet.

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“…Thus, a combination of radiation therapy with T cell-based immunotherapy appears to be logical and feasible especially when bearing in mind that radiotherapy can increase the local expression of multiple cytokines including for example interferons as well as homing factors such as the chemokines CXCL9-11, CXCL10, and CXCL11. In addition, radiation may also affect the tumor blood vessels, and cause an upregulation of adhesion molecules thereby favoring the invasion of immune cells into the tumor tissue and improving the local conditions of the tumor microenvironment for immunotherapy (e.g., [ 20 , 21 ]).…”

Section: Introductionmentioning

confidence: 99%

Combining Radiation- with Immunotherapy in Prostate Cancer: Influence of Radiation on T Cells

Lindner

Arndt

Loureiro

et al. 2022

IJMS

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Radiation of tumor cells can lead to the selection and outgrowth of tumor escape variants. As radioresistant tumor cells are still sensitive to retargeting of T cells, it appears promising to combine radio- with immunotherapy keeping in mind that the radiation of tumors favors the local conditions for immunotherapy. However, radiation of solid tumors will not only hit the tumor cells but also the infiltrated immune cells. Therefore, we wanted to learn how radiation influences the functionality of T cells with respect to retargeting to tumor cells via a conventional bispecific T cell engager (BiTE) and our previously described modular BiTE format UNImAb. T cells were irradiated between 2 and 50 Gy. Low dose radiation of T cells up to about 20 Gy caused an increased release of the cytokines IL-2, TNF and interferon-γ and an improved capability to kill target cells. Although radiation with 50 Gy strongly reduced the function of the T cells, it did not completely abrogate the functionality of the T cells.

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Prevalence of mismatch repair genes mutations and clinical activity of PD-1 therapy in Chinese prostate cancer patients

Fang

Zeng

et al. 2022

Cancer Immunol Immunother

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Prostate cancer (PCa) patients with mismatch repair (MMR) genes mutations are potentially responsive to immune checkpoint blockade (ICB). However, aberrations in MMR genes were rare in PCa and there is evidence that MMR genes mutations are highly ethnic-speci c. Thus, the prevalence and clinical characteristics of this subgroup in Chinese PCa patients are largely unknown. Furthermore, why some of these patients do not respond to ICB also remains unclear. Here, we analyzed the sequencing data from 3338 Chinese PCa patients to pro le the mutation spectrum of the MMR genes. We found that in metastatic disease, the pathogenic mutation frequency of MMR genes in Chinese PCa patients was higher than that in the Caucasus population (4.8% vs 2.2%, P = 0.006) and the mutation carriers responded poorer to androgen deprive therapy (ADT) and abiraterone than non-carriers. Besides, we reported a multi-institutional cases series of 11 PCa patients with mismatch repair de ciency (dMMR) or microsatellite instability-high (MSI-H) who received programmed cell death receptor-1 (PD-1) inhibitors, and performed multiplex immunohistochemistry (mIF) to explore the relationship between tumor immune microenvironment (TIME) and response to ICB. The results showed that the responders had higher density of intratumoral CD8 + T cells than non-responders. Our data suggested MMR genes mutations may be more common in Chinese PCa patients and it is associated with poorer response to hormonal therapies. We propose that the density of intratumoral CD8 + T cells could be a promising predictor to help further subdivide the population of PCa patients who can bene t from immunotherapy.

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Overcoming Immune Resistance With Radiation Therapy in Prostate Cancer

Cited by 7 publications

References 168 publications

The functions and mechanisms of RNA modification in prostate: Current status and future perspectives

The functions and mechanisms of RNA modification in prostate: Current status and future perspectives

Combining Radiation- with Immunotherapy in Prostate Cancer: Influence of Radiation on T Cells

Prevalence of mismatch repair genes mutations and clinical activity of PD-1 therapy in Chinese prostate cancer patients

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