As the weather gradually turns cooler, do tumors also respond to temperature changes?

As the weather gradually turns cooler, do tumors also respond to temperature changes?

With the crisp autumn wind blowing and a hint of chill in the air, it's the perfect time to discuss the "hot and cold" mechanisms of tumors. While it's well known that tumors can be classified as "benign" or "malignant," not many are aware of the distinction between "hot" and "cold" tumors. What are the differences between these two types of tumors, and how do their treatments differ? In the following, I will introduce "cold" tumors and "hot" tumors to you!

1. What are cold tumors and hot tumors?

Cold tumors and hot tumors are clinically proposed classification concepts based on their response to immunotherapy. First of all, you must know that a tumor is not a bunch of cancer cells. It contains not only cancerous cells, but also many symbiotic normal cells, such as vascular cells, immune cells, etc. Among them, immune cells are the most familiar "health guardians" that can compete with cancer cells. Whether the combat effectiveness of immune cells can be stimulated in the anti-tumor process is an important dimension to evaluate the probability of defeat in this vicious battle.

Figure 1

Just imagine if there are more immune cells in the tumor, and each one is responsive, well-trained, and cooperative, then this war will be fierce. Then we can simply understand this type of tumor as a hot tumor.

On the contrary, if there are not many immune cells in a tumor and most of them are sick and disabled, everyone probably already knows the probability of winning this battle. Then we can understand this type of tumor as a cold tumor.

Figure 2

2.What are the common cold tumors and hot tumors?

Currently, in clinical practice, there is no fixed standard for how to judge the "cold" or "hot" of a tumor. Common methods include PD-L1 staining, tumor infiltrating immune cell analysis, tumor comprehensive immune score assessment, gene mutation analysis and other methods.

According to previous research or clinical treatment responses, common cold tumors include glioblastoma, prostate cancer, ovarian cancer, and pancreatic cancer.

Tumors considered hot include bladder cancer, head and neck cancer, kidney cancer, liver cancer, melanoma and non-small cell lung cancer, as well as various types of tumors with high rates of microsatellite instability.

Of course, hot and cold tumors are not fixed based on the type of cancer, and it depends on the patient's personal situation.

Studies have found that immune checkpoint inhibitors work better against "hot" tumors. This is natural because these drugs target immune cells present in tumors. These drugs are less effective in "cold" tumors because there are few or no such cells.

3.How to transform cold tumors into hot tumors?

From a biological perspective, the "cold" mechanism of tumors can be explained simply as follows:

1. Lack of Tumor-Specific Antigens: "Cold" tumors often lack specific markers or antigens that can alert the immune system to their presence. It's like having very few enemy soldiers, and as a result, the immune cells lack the enthusiasm to mount an attack.

2. Antigen Presentation Deficiency: In "cold" tumors, even if there are enemy soldiers (antigens) present, our immune system's reconnaissance team may fail to detect their existence effectively. This situation is akin to being unable to initiate a battle because we haven't located the enemy.

3. Impaired T Cell Trafficking and Infiltration: T cells, which are like our army, might be slow to mobilize, have trouble reaching the battlefield, or move too slowly within the tumor, leading to obstacles in engaging the enemy within.

4. T Cell Dysfunction or Death: Even if our army arrives at the enemy's territory and locates the enemy soldiers, they may find that they have lost their initial combat effectiveness or have even perished, making it difficult to fight back effectively.

5. Other Tumor Microenvironment Factors: Various factors in the tumor's microenvironment, such as unfavorable conditions or interference from external factors, can also impact the success or failure of the battle.

Figure 3

4.Will immunotherapy be functional if one has cold tumors?

It is generally believed that patients with "cold" tumors often have suboptimal responses when treated with immunotherapy alone. In line with the principle of not giving up, efforts are made to transform "cold" tumors into "hot" tumors, as only then can there be a chance for the immune cells to regain their fighting capabilities.

5.How to transform cold tumors into hot tumors?

To "awaken" a "cold" tumor, the most crucial aspect is to make it "hot," which means ensuring that there are enough antigens on the surface of tumor cells to effectively activate the immune system. Scientists have come up with various methods in the hope of transforming "cold" tumors into "hot" tumors, such as radiotherapy, chemotherapy, targeted therapies, DNA repair-based therapies, CAR-T therapy, oncolytic viruses, tumor vaccines, T cell immune modulators, and more. Some combination treatment approaches have also shown initial success. Therefore, with the continuous progress of scientific research, the transformation from "cold" to "hot" tumors is not impossible.

Summary

Cancer treatment has always been a focal point of clinical research, and the rapid development of immunotherapy in recent years has provided confidence and hope in the fight against cancer. While not everyone currently benefits from immunotherapy, it is believed that as scientific research progresses and reliable testing technologies mature, more individuals will be identified who can benefit from immunotherapy.

References

[1]Turning Cold into Hot: Firing up the tumor Microenvironment[J].Trends Cancer. 2020 Jul;6(7):605-618.

[2]Turning cold tumors hot: from molecular mechanisms to clinical applications[J]. Trends in immunology, 2022(7):43.

Statement: This article is for sharing only and does not represent the position of the platform. If there are copyright and other issues involved, please contact us as soon as possible and we will correct it as soon as possible. Thank you!