Release date: 2017-06-22

In recent years, immunotherapy is an emerging cancer treatment technology that attacks tumor cells, attracting the imagination of the public. When it works, the results are amazing. However, under normal circumstances, scientists still do not know why this works.

Published in the journal Nature Immunology on June 19, 2017, researchers at the La Jolla Institute of Allergy and Immunity found that T cell subsets in tumors called tissue resident memory T cells (TRM) are An important distinguishing factor between cancer patients. Their discovery was to identify gene expression patterns of cytotoxic T cells isolated directly from patient tumors from the first large-scale effort.

"The systematic study of immune cells from cancer patients reveals a lot of information," said Associate Professor LJI and Dr. Pandurangan Vijayanand, distinguished professor of William K. Bowes Jr., and Professor Christian Ottensmeier to guide the study. Vijayanand added: "This may be a benchmark to predict whether a patient will respond to immunotherapy and guide the most likely effective immunotherapy options, which is almost like evaluating tumor immunity. Tumor invasive T cell system The analysis will also provide new insights into their underlying biology and reveal new potential immunotherapeutic drug targets.

Scientists have initially discovered that when T cells accumulate in a patient's tumor, the patient lives longer. However, over time, they found that T cells lost their enthusiasm and cancer cells prevailed. In the past decade, they have discovered why: inhibitory molecular signals emanating from tumors or their environment weaken the immune response, making tumor cells invisible to the immune system. A class of cancer immunotherapeutics called checkpoint blockade inhibitors can make PD-1 or CTLA-4 two known molecules that enable cancer cells to survive and reproduce through the immune system.

Dr. Anusha-Preethi Ganesan, the first author of the study, said, “The challenge with immunotherapy based on PD-1 and CTLA-4 is that if they work, they miraculously work, but they can only be in about 30% of patients. Effective. "If we are doing all these immunotherapy based on activating T cells to kill tumor cells, then knowing what the transcriptional profiles of these T cells are, what molecules they produce are very important.

To reveal potential causes of little or no benefit to patients and to identify the patients most likely to respond, Ganesan uses advanced genomics tools to define the molecular characteristics of a powerful anti-tumor immune response using freshly resected tumors from cancer patients. . Gene expression profiles of cytotoxic T cells (CTLs) isolated from 41 head and neck tumors and 36 untreated early lung tumors were compared to CTLs isolated from adjacent normal lung tissues. Ganesan identified different tumor types. A shared molecular fingerprint, indicating extensive reprogramming of CTLs infiltrating tumor tissue.

In addition to their shared molecular features, tumor invasive CTLs vary widely in the expression of molecules associated with T cell activation and known immune checkpoints. "There is a lot of heterogeneity, which has a big impact on immunotherapy," Ganesan said. “We saw traditional immunotherapy goals, but they were not expressed in every patient, which means that not every patient is currently a candidate for immunotherapy for PD-1 or CTL4-1, so Having a complete transcriptional profile is so important to understanding the complexity of the entire immune network and identifying new targets."

Interestingly, the gene expression pattern indicating the presence of tissue resident memory T cells (TRM) corresponds to better anti-tumor activity. Large-scale analysis of 689 lung cancer patients in an independent cohort confirmed that patients with high-density TRM cells in tumor tissue prolonged survival, suggesting that these cells play a key role in protecting tumor recurrence.

Vijayanand said: "Any time you remove the tumor, the patient is a ticking time bomb, some people will relapse, while others will not." "Our research shows that the presence of these tissue resident memory cells is a certain Whether a person has an effective immune response to cancer and whether it has a longer life span."

Source: Noble

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