Prostate cancer: a mechanism that suppresses the immune system has been discovered

Italian study identifies two microRNAs carried by tumour vesicles that alter the behaviour of macrophages: a new avenue for understanding resistance to immunotherapy

by Giuseppina Catanzaro*

6 November 2026

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3' min read

Translated by AI

Versione italiana

Key points

Why does prostate cancer respond so poorly to immunotherapy?
Two microRNAs are transported in extracellular vesicles
The study involving 79 people and the link to tumour grade
Blocking microRNAs restores anti-tumour properties
Liquid biopsy: possible future applications
From laboratory discovery to treatments

3' min read

Translated by AI

Versione italiana

Prostate cancer can weaken the immune system through molecular signals travelling in the blood. Italian research has identified two microRNAs, miR-302a-5p and miR-367-3p, capable of steering macrophages towards a state that is more tolerant of the tumour. In laboratory experiments, interfering with these signals has made it possible to restore certain characteristics of immune cells associated with combating the tumour.

This discovery helps us to understand one of the mechanisms that may contribute to the limited response of prostate cancer to immunotherapy. Whether this can be developed into an effective treatment for patients remains to be seen.

The study, published in the *Journal of Experimental & Clinical Cancer Research*, is the result of a collaboration between Link University, the CNR Institute of Translational Pharmacology, IRCCS LIFE Santa Lucia, Sapienza University of Rome and Policlinico Umberto I.

Why does prostate cancer respond so poorly to immunotherapy?

Immunotherapy aims to enhance the immune system’s ability to recognise and combat cancer cells. In prostate cancer, it often encounters an environment that is not conducive to the activation of an effective response, known as a ‘cold’ tumour microenvironment.

Macrophages, immune cells capable of altering their behaviour in response to the signals they receive, play a significant role. To describe this plasticity, researchers distinguish between M1-type characteristics, associated with an inflammatory and anti-tumour response, and M2-type characteristics, linked to tissue repair and the regulation of immunity.

These are functional mechanisms, with numerous intermediate stages. The tumour can exploit this flexibility by promoting cellular states that suppress the immune response.

Two microRNAs are transported in extracellular vesicles

At the heart of the study are extracellular vesicles, tiny membrane-bound structures that transport biological material between cells.

In the experiments, prostate cancer cells released vesicles enriched with miR-302a-5p and miR-367-3p. These microRNAs are short RNA molecules that help regulate gene activity. Carried by the vesicles, they can alter the functional programme of macrophages, promoting M2-type immunoregulatory characteristics.

Vesicles isolated from patients’ plasma also reproduced this effect. By reducing the levels of the two microRNAs in the vesicles produced by the tumour cells, the researchers observed a shift towards M1-like characteristics.

The study involving 79 people and the link to tumour grade

The study involved 79 people undergoing investigations for suspected prostate cancer at the Policlinico Umberto I: 59 were diagnosed with cancer and 20 had a negative biopsy result. This was an observational cohort recruited from a single centre.

Monocytes – the precursors of macrophages – were isolated from the blood and then allowed to mature in the laboratory. In samples from cancer patients, the macrophages obtained in this way showed a greater tendency to acquire M2-type characteristics. This tendency was found to be associated with the histological grade of the tumour.

The findings suggest that circulating signals may influence immune precursors. The authors point out, however, that the experiments do not demonstrate that the entire reprogramming programme is already present in monocytes whilst they are circulating in the body.

Blocking microRNAs restores anti-tumour properties

To investigate the role of the two molecules, inhibitors based on LNA (Locked Nucleic Acid) technology were used: short sequences of nucleic acids modified to bind to the target microRNAs and inhibit their activity.

The combined inhibition of miR-302a-5p and miR-367-3p caused patient-derived macrophages to revert to M1-like characteristics, even in samples associated with high-grade tumours.

This provides experimental evidence that it is possible to influence the mechanism. Further studies will be needed to establish whether the restoration of cellular markers and functions is linked to an actual ability to control the tumour.

Liquid biopsy: potential future applications

The presence of these markers in the blood makes the prospect of liquid biopsy – that is, the analysis of circulating biological material to obtain information about the disease – a promising one. Identifying this molecular code could, in future, help to identify patients who are suitable candidates for cell reprogramming strategies to be used alongside existing treatments.

However, this possibility needs to be validated: the study does not introduce a new blood test that can already be used to diagnose the cancer or predict the response to immunotherapy.

From laboratory discovery to treatments

The aim is to develop treatments capable of reaching the target cells and selectively modifying their behaviour. This will require in vivo studies, safety assessments and suitable delivery systems for the inhibitors. The study provides evidence of the biological mechanism, whilst its therapeutic applicability remains to be established.

*Associate Professor at Link University