“Cold Behaviour” Not Just a Human Quirk

Leela Maitreyi

February 05, 2020

Hot, cold, and medium. No. We are not talking about how you would like your Coffee Latte but how hot or cold tumors can be.

Tumors come in all shapes, sizes and forms — some better targets for treatments than others. Despite blockbuster success of immunotherapy in the recent years, there are therapeutic limitations that are boggling scientists and clinicians worldwide. One of which is the nature of immune behaviour of tumors- HOT or COLD.

What are HOT Tumors?

These are those tumors that have already been infiltrated by T cells. Such tumor cells have undergone many mutations that create neoantigens recognized by the T cells. With the presence of cancer-fighting T cells, the immune system has already recognized the cancer and is working to fight it. For this reason, hot tumors respond well to immunotherapy treatment using checkpoint inhibitors.The main idea behind checkpoint inhibitors is using antibodies to mobilize the T cell response through pathways that cause a favourable interaction between a tumor and T cell. Only a few types of cancers are considered to be hot — melanoma, bladder, kidney, head and neck, and non-small cell lung cancer.

However, not every hot tumor in every patient is responsive to such treatments.

What are COLD Tumors?

Non-immunogenic or “cold” tumors are those that have not yet been infiltrated with T cells, a sign that the immune response is not working. 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. These tumors pose major therapeutic challenges to immunotherapy.

Can there be a switch from “Cold” to “Hot”?

How can the response to an immunotherapy be improved and maintained in both immunologically cold and hot tumors?

Proof of principle studies have shown that one can combine conventional therapies with checkpoint inhibitors to make them work better and turn immunologically cold tumors into hot ones.

Does chemotherapy in conjunction with checkpoint inhibitors stimulate a potent immune response in patients with cold tumors?

It appears that giving standard doses of chemotherapy along with checkpoint inhibitors may be the optimal way to spur the immune T cells into action.

This leaves us with the question:

“Will classical cytotoxic chemotherapy remain the mainstay of treatment whether in isolation or in combination with such new and stellar therapies?”