Immunology for Non-Immunologists: Hot vs. Cold Tumors

Hot, cold, and in-between. Tumors come in all forms — some better targets for immunotherapy treatment than others. This post will help you learn more about hot tumors, cold tumors, and what researchers are doing to make cold tumors more receptive to immunotherapies. 

Image from the Dana-Farber Cancer Institute. Image Source.

What Are Hot Tumors? 

Tumors described as “hot” are those that show signs of inflammation, meaning the tumor has already been infiltrated by T cells rushing to fight the cancerous cells. The tumor cells have undergone many mutations that create neoantigens recognized by the T cells. 

With the presence of cancer-fighting T cells, we know that the immune system has already recognized the cancer and is working to fight it. For this reason, hot tumors typically respond well to immunotherapy treatment using checkpoint inhibitors, like the mechanism deployed by Keytruda, Opdivo, and Yervoy.

The main idea behind checkpoint inhibitors is using antibodies to mobilize the T cell response.  During the attack on the tumor, T cells become exhausted and lose important functions needed to kill tumor cells. The exhaustion is brought on by constant exposure to tumor antigens and signalling through checkpoint receptors.  The antibodies block signalling through these receptors to prevent this loss of function. You can read more about our research on PD-1 blockades here.

Only a few types of cancers are considered to be hot — including melanoma, bladder, kidney, head and neck, and non-small cell lung cancer — and further limiting the efficacy of immunotherapies is the fact that not every hot tumor in every patient will be responsive to such treatments. 

To combat these limitations, research is focusing on combining progressive immunotherapy treatments with traditional therapies like radiation and chemotherapy.

What Are Cold Tumors?

In contrast, nonimmunogenic “cold” tumors have not yet been infiltrated with T cells, a sign that the immune response is not working for one reason or another. The lack of T cells makes it difficult to provoke an immune response with immunotherapy drugs. 

These types of tumors are mostly treated with traditional cancer therapies. Most breast cancers, ovarian cancer, prostate cancer, pancreatic cancer, and glioblastomas are typically cold tumors, which poses a problem for the widespread use of immunotherapies. 

The microenvironment surrounding cold tumors contains myeloid-derived suppressor cells (MDSC) and T regulatory cells (Tregs), which are known to dampen the immune response and inhibit T cells trying to move into the tumor.

How to Turn Cold Tumors Hot

Because of the resistance of cold tumors to immunotherapy drugs, much research has been done recently to understand if and how we can “switch” cold tumors to hot. The goal of such research is to essentially reverse the suppressive microenvironment surrounding cold tumors and attract more of the right anti-tumor lymphocytes to battle the cancer. 

This review article published in Frontiers in Immunology in February 2019 offers an excellent discussion of the potential therapeutic approaches and the issues that could be encountered by the immune system, including a lack of tumor antigens, a defect in antigen-presenting cells, and the absence of T cell activation.  

Learn more about just some of the research being done in this arena:

Where Is Your Cancer Research Taking You?

Whether you’re developing innovative immunotherapies, researching the tumor microenvironment, of studying other important aspects of fighting this deadly disease, we support you! 

Check out our tumor-specific T cells and other antigen-specific T cells, or let us know if we can develop a custom cell line for you.

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