Chinese scientists develop new technology to decode immunotherapy resistance in tumor microenvironment

Chinese scientists have established a new technology platform that reveals how genetic mutations in tumors reshape the microenvironment and modulate immune responses, a discovery that could explain why modern cancer treatments often fail in patients whose cancers have spread.

The study, published in the journal Cell on Thursday, was jointly conducted by a Shanghai-based team from the Center for Excellence in Molecular Cell Science at the Chinese Academy of Sciences, in collaboration with teams from Shanghai Jiao Tong University, and Guangzhou Laboratory.

Using the new technology platform called CLIM-TIME (CRISPR-Laser-captured microdissection Integration Mapping of Tumor Immune Microenvironment), the researchers analyzed 391 common tumor suppressor genes to see how they reshape the tumor microenvironment — the biological neighborhood surrounding a tumor, and classified them into seven distinct subtypes.

The researchers found that the loss of certain tumor suppressor genes — genes that normally prevent cancer growth — triggers a massive buildup of collagen. This excess collagen makes the tumor structure so dense that it acts like a wall, preventing T cells — the body's natural "assassin" cells — from reaching and killing the cancer.

"It acts like a spider weaving a web. This web not only supports itself but also recruits and reshapes other normal cells from the body into accomplices that help shape this suppressive environment, blocking T cells' entry," said Wang Guangchuan, researcher at the Center for Excellence in Molecular Cell Science.

The team identified a specific molecule called LOXL2 as the architect of this barrier. In tests on mice, researchers found that by blocking LOXL2, they could dissolve the collagen wall. This allowed T cells to penetrate the tumor and significantly boosted the power of immunotherapy drugs.

We combined this with current CAR-T cell therapy. One major issue with CAR-T is that it can't enter solid tumors. When treating human tumors with CAR-T, if we use a small molecule to target this protein we've identified, it could significantly improve CAR-T treatment outcomes. Of course, when it comes to clinical application, we still need to evaluate its safety [and other indicators]," Wang said.

CAR-T is an immunotherapy involving the genetic engineering of a patient's T-cells to recognize and attack cancer cells.

Chinese scientists develop new technology to decode immunotherapy resistance in tumor microenvironment

A Chinese envoy said on Monday that the international community must make every effort to promote a ceasefire in Sudan.

Speaking at a UN Security Council meeting on Sudan, Sun Lei, China's deputy permanent representative to the United Nations, said the international community should persistently pursue peace talks, alleviate the humanitarian crisis, and stand together to maintain regional stability.

"As the conflict in Sudan drags on, it has not only caused heavy casualties and displacement of ordinary people, but also severely undermined development of the country and impacted the stability of neighboring countries. This tragedy should not continue. The Sudanese people's desire for peace is growing, and the responsibility of the UN Security Council and the international community is becoming even greater. China has consistently stressed that sanctions are a means, not an end, and should not become a substitute for diplomatic efforts. The UN Security Council should use this special tool prudently, fully respect Sudan's sovereignty, take into account the legitimate concerns of the country concerned, and ensure that sanctions are objective, just and effective," said Sun.

China welcomes the Sudanese government's initiation of an inclusive political dialogue and supports the United Nations in playing its central mediation role, Sun said.

The international community should effectively safeguard Sudan's sovereignty, unity and territorial integrity, adhere to the principle of Sudan's ownership, and avoid imposing external solutions, he added.

Since erupting on April 15, 2023, the war in Sudan has killed tens of thousands, displaced millions, and ruined the economy.

Politically, Sudan is deeply divided, with an internationally recognized government aligned with the Sudanese Armed Forces (SAF), and a parallel administration declared by the paramilitary Rapid Support Forces (RSF) in alliance with political and armed groups.

Analysts warn that this fragmentation of authority is prolonging the conflict and raising fears of further instability.

China calls for all-out efforts to promote ceasefire in Sudan