Five Phases of the Underlie Immunotherapy Response

Five factors predict response to chemotherapy inhibitor (CPI) in many types of cancer, research shows.

Investigations, at Nature Geneticscan personalize cancer treatment by identifying people most likely to benefit from immunotherapy.

They may also expand the use of immunotherapy, as several groups of patients who would otherwise not be considered candidates were identified as likely to benefit from the treatment.

The researchers believe that these five components form a reference framework for current and future biomarkers of CPI response and survival.

“Until now, most studies have focused on identifying and reporting individual biomarkers, but our results suggest that many of these biomarkers may be different types of the same reasons,” said researcher Abel González-Pérez, PhD, a bioinformatics expert from The Barcelona Institute. of Science and Technology in Spain.

CPIs have made a significant impact in cancer treatment but patient response varies widely, and treatment can cause immune-related adverse events.

It is becoming increasingly clear that CPI response and survival are influenced by underlying factors including characteristics of the tumor, its microenvironment, and the host.

Biomarkers identified in different studies may in fact represent different measures of these tumor subtypes, making it difficult to determine how many independent markers there are.

For example, the expression of genes and genes that were known as biomarkers can jointly represent the degree of penetration of cytotoxic cells into the tumor.

To investigate further, the researchers studied thousands of molecular and clinical features in 479 patients with metastatic tumors who were part of the Center for the Study of Cancer Treatment.

Participants received anti-PD1/PDL1 or a combination of anti-PD1/PDL1 and anti-CTLA4 therapy.

Analysis of genomics, transcriptomics and clinical data revealed that all highly correlated features fell into one of five independent factors associated with all tumor types.

These were: tumor mutational burden (TMB); effective infiltration of T cells; whether patients received any prior treatment; the activity of transforming growth factor-beta (TGF-β) in the tumor microenvironment; and the ability of the tumor to spread.

Their relationship with the CPI response and survival have been confirmed in six independent groups, with 1491 people, who have taken six major types of cancer.

The researchers evaluated how five latent factors combined using multiple machine learning models to predict response, overall survival or progression-free survival in the first group of patients.

When applied to patients in the HMF group who did not receive CPIs, this revealed a significant proportion of patients with skin (35%), bladder (42%) and lung tumors (16%) who they may respond to treatment. .

Patients with other metastatic diseases, some of whom would not be considered candidates for CPI, were also identified as potential responders.

For example, 4% of breast cancer patients, 3% of those with colorectal cancer, 19% of those with kidney tumors, and 15% of those with liver cancer showed a high probability of responding to CPI .

“This study represents an important step in understanding how different tumor characteristics affect treatment response,” said researcher Nuria Lopez-Bigas, PhD, who is also from The Barcelona Institute of Science and Technology.

“In the future, we hope that these five factors will be integrated into clinical practice to guide treatment decisions.”