Combating cancer by boosting immunity and disrupting the tumor microenvironment

Asha Palat and Brandon Mistretta are researching new approaches in the battle against cancer, with Mistretta equipping the immune system with the means to to detect tumors and Palat targeting the tumor microenvironment, a strategy they believe is crucial for effective treatment. 

Despite their diverse origins, Mistretta from Buffalo, New York, and Palat from Chennai, India, share a personal connection to the disease."Whether it’s you or someone you care about, it will change your world," reflects Mistretta, inspired by a college roommate's cancer battle.  

“Having seen someone I care about go through cancer treatment, and the hardships he faced while doing it, I know how important it is to have better therapy options out there.” 

Both Mistretta and Palat joined Dr. Preethi Gunaratne's lab, known for its work on the National Cancer Institute’s Human Cancer Genome Atlas. Palat emphasizes the innovative aspect of their research: “Most cancer therapy approaches look at the tumor, not the microenvironment it grows in,” explains Palat. “By targeting the microenvironment, we have the opportunity to come up with therapies that can maybe even prevent cancer from occurring in the first place.” 

While conventional treatments like chemotherapy can be effective in the earliest stages of cancer, they often don’t work as well with more advanced disease and a lot of patients don’t respond to these treatments at all. And the side effects – ranging from nausea to heart complications – can be daunting.  

“What’s needed are new therapies that don’t take that large of a toll on a person,” Mistretta says. “the main problem with chemotherapy is we are not seeing the success rates that we want, as well as it being a very harsh living situation for the patient. It also targets every cell in your body, so if you have a tumor cell, it can now progress to cancer even more because of the toxins that you are adding to your system.”

Mistretta’s angle: A focus on T-cells

In search of alternatives to chemotherapy, Mistretta is delving into the potential of leveraging the patient's immune system to fight cancer. 
 
His attention is particularly centered on T-cells, the potent immune cells tasked with combating various threats and damaged cells, including tumor cells. "Approximately one-third of the population will develop a cancer," he notes.  

"Two-thirds won't because their immune systems are doing their job. We think, for those who are getting cancer, it is most likely due to the fact that T-cells can't get into the tumor microenvironment. So I’m using NGS techniques to try to determine if there are T-cells that match the tumor cells in the body – and we think there are – and if so, how we could assist them into the tumor microenvironment so they can get to work." 

One significant hurdle in his research is dealing with cancer samples preserved in formalin-fixed paraffin-embedded (FFPE) blocks, which complicates the extraction of high-quality RNA. "FFPE blocks make the quality of RNA we can extract out pretty poor, which directly affects our sequencing," Mistretta explains.  

The challenge is exacerbated by the presence of unwanted RNA species, making RNA sequencing more complex. However, he highlights the use of the QIAseq FastSelect RNA Removal Kit as a pivotal tool in his arsenal, enabling efficient removal of unwanted RNA, thus improving the sequencing process. "Fifteen minutes later, we are ready to prep the samples." 

This kit is part of QIAGEN's comprehensive RNA-seq technologies suite, facilitating a higher throughput of samples without compromising data quality.

Palat’s angle: The tumor microenvironment

Palat is pursuing a distinct approach in her research, focusing on disrupting the tumor microenvironment to starve cancer cells of the nutrients essential for their growth and proliferation.  

"While Brandon’s work focuses on equipping the immune system with the means of tracking down the tumor and attacking it, I’m trying to directly intercept signals in the microenvironment to make the tumor more vulnerable for any kind of cancer therapy," Asha states confidently.  

She employs a microRNA drug to diminish the tumor's glucose absorption, a critical factor for the cells' proliferation and metastasis.  “These cells rely heavily on glucose to proliferate and metastasize,” she explains.  

By targeting the tumor cell's energy intake, Palat aims to weaken the cells, rendering the tumor microenvironment more susceptible to the immune response Mistretta is working to bolster.  

Their collaborative efforts in tackling cancer from both the immune system enhancement and microenvironment disruption perspectives hold promise for developing universal immunotherapies. 

"If we can target cell metabolism to sensitize tumors to treatment, we can do that for all types of tumors," Palat asserts. She emphasizes the potential broad applicability of their strategies, contrasting with the current cancer therapies that are often limited to specific cancer types or mutations.

Advancing RNA Studies

Both Mistretta and Palat use QIAGEN’s suite of products in their research, and particularly highlight the use of RNA and DNA extraction kits, the QIAcube, and various library preparation kits. A standout in their toolkit is the QIAseq FastSelect RNA Removal Kit, which Mistretta praises for its transformative impact on his work. 

“Once QIAseq FastSelect is introduced, you are able to mix that with your RNA from the cells and it depletes all the ribosomal RNA that’s clogging up the system, vastly improving your results,” Mistretta explains. He further appreciates the kit’s user-friendliness and efficiency, stating, “It’s incredibly easy to use too. It takes no time to add to a sample and then a quick 15-minute reaction takes care of all that ribosomal RNA. Using this kit saves me easily eight hours of benchwork, which allows us to be super high-throughput on our samples.” 

Palat, on the other hand, emphasizes the quality of RNA extracted using QIAGEN kits, crucial for her work where sample volume is limited. “Nothing else matches the consistency, quality, and concentration of RNA that I get from these kits,” she asserts. “And that’s important because, after treatment, I don’t have a lot of samples from which to collect the RNA. I need to efficiently extract it and know that I’ll have quality at the end.” 

The integration of QIAGEN products into their workflow not only augments the quality and efficiency of their research but also propels Mistretta, Palat, and their colleagues towards their goal of developing more humane cancer treatments. The commitment of the team in Gunaratne lab to improving cancer therapeutics is clear, with Mistretta sharing his personal motivation: “If I can translate my work into a viable therapy, it would be incredibly rewarding.”