Help us: Donate
Follow us on:



Manipulating the Immune System for Cancer Immunotherapy


Researchers have manipulated the immune system to respond more aggressively to cancer, according to a new study [1].

Manipulating macrophages

We have discussed modulating the immune system multiple times recently, especially in regards to macrophages and manipulating their behavior. Macrophages are part of the innate immune system and carry out a wide variety of tasks, such as clearing away cell debris, engulfing pathogens, facilitating tissue growth, and disposing of senescent cells once other immune cells have destroyed them.

Macrophages have a certain behavioral pattern that determines how they act and respond to stimuli; this is known as polarization. The polarization of macrophages can be broadly divided into two types, M1 and M2, although this is a simplification of what is actually a subtle range of states.

In broad terms, the M1-type macrophages are proinflammatory and aggressive, while the M2-type macrophages favor anti-inflammatory activity and focus on tissue repair following injury. In order for the immune system to function properly, a suitable balance between these two polarizations is required. When that balance is disrupted and the ratio of M1 and M2 macrophages is wrong, this can lead to problems.

Having too many M1 types and too few M2 leads to excessive inflammation and contributes to many age-related inflammatory conditions. Therefore, recent focus has moved to manipulating the ratios of M1 and M2 macrophages to combat various diseases.

In the case of age-related inflammatory conditions, the ratio needs to shift towards a more healing profile, so more M2 macrophages need to be encouraged to facilitate tissue healing and repair. This leads to a healing environment that favors reduced inflammation, which, for those conditions, is good.

However, in the case of cancer, the opposite is desirable; the more M1-type macrophages in the cancer environment there are in the short term, the more aggressively it can be fought. These researchers have focused on increasing the number of M1 macrophages, and they have presented some promising results.

Effectively activating macrophages that can ‘eat’ cancer cells is challenging. In particular, cancer cells secrete macrophage colony stimulating factor (MCSF), which polarizes tumour-associated macrophages from an antitumour M1 phenotype to a pro-tumorigenic M2 phenotype. Also, cancer cells can express CD47, a ‘don’t eat me’ signal that ligates with the signal regulatory protein alpha (SIRPα) receptor on macrophages to prevent phagocytosis. Here, we show that a supramolecular assembly consisting of amphiphiles inhibiting the colony stimulating factor 1 receptor (CSF-1R) and displaying SIRPα-blocking antibodies with a drug-to-antibody ratio of 17,000 can disable both mechanisms. The supramolecule homes onto SIRPα on macrophages, blocking the CD47–SIRPα signalling axis while sustainedly inhibiting CSF-1R. The supramolecule enhances M2-to-M1 repolarization within the tumour microenvironment, and significantly improves antitumour and antimetastatic efficacies in two aggressive animal models of melanoma and breast cancer, with respect to clinically available small-molecule and biologic inhibitors of CSF-1R signalling. Simultaneously blocking the CD47–SIRPα and MCSF–CSF-1R signalling axes may constitute a promising immunotherapy.


As our understanding of the immune system grows and our ability to manipulate it towards more favorable activity increases, we take further steps towards combating diseases by using our own cells.

As we age, the immune system becomes increasingly dysfunctional due to inflammation from various sources, so controlling that inflammation and manipulating our immune system to work better are promising avenues of research in the fight against cancer and aging.


[1] Ashish Kulkarni, Vineethkrishna Chandrasekar, Siva Kumar Natarajan, Anujan Ramesh, Prithvi Pandey, Jayashree Nirgud, Harshangda Bhatnagar, Driti Ashok, Amrendra Kumar Ajay & Shiladitya Sengupta. A designer self-assembled supramolecule amplifies macrophage immune responses against aggressive cancer (2018) Nature Biomedical Engineering.

About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 600 articles on the topic, interviewed over 100 of the leading researchers in the field, hosted livestream events focused on aging, as well as attending various medical industry conferences. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Swiss Monthly, Keep me Prime, and New Economy Magazine. Steve is one of three recipients of the 2020 H+ Innovator Award and shares this honour with Mirko Ranieri – Google AR and Dinorah Delfin – Immortalists Magazine. The H+ Innovator Award looks into our community and acknowledges ideas and projects that encourage social change, achieve scientific accomplishments, technological advances, philosophical and intellectual visions, author unique narratives, build fascinating artistic ventures, and develop products that bridge gaps and help us to achieve transhumanist goals. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project.
  1. jimofoz
    July 4, 2018

    Cancer cells can also over express MHC class 1 to avoid phagositosis by macrophages:

Write a comment:


Your email address will not be published.

This site uses Akismet to reduce spam. Learn how your comment data is processed.

You have 3 free articles remaining this week. You can register for free to continue enjoying the best in rejuvenation biotechnology news. Already registered? Login here.