Paris (AFP)

Small structures around tumors play an important role in the immune response to cancer and could help predict the effectiveness of treatment with immunotherapy, highlighted several teams of researchers.

Immunotherapy drugs, which seek to trigger an immune response of the body against cancer cells, have revolutionized the management of cancers in recent years. However, they are often only effective in a minority of patients (25% on average), with wide disparities from one type of cancer to another.

Identifying markers predicting the response to this type of treatment is therefore a key issue, in particular to avoid unnecessarily exposing patients to their toxicity.

Until today, this strategy focused mainly on T lymphocytes, the white blood cells responsible for recognizing and attacking infected or cancer cells.

But three studies published simultaneously on Wednesday in the scientific journal Nature conclude that cell aggregates in the immediate environment of tumors, called tertiary lymphoid structures (SLT), could also be good markers of the effectiveness of immunotherapy.

These cell aggregates, which are not present in all tumors, are rich in B lymphocytes, the white blood cells that produce antibodies.

Tertiary lymphoid structures function as "factories or schools" where immune cells learn to recognize cancer cells, Wolf Fridman, emeritus professor of immunology at the University of Paris, told AFP. the first of these studies.

By analyzing 600 tumors of patients with soft tissue sarcoma, the researchers observed that an "anti-tumor immune response was initiated" within these structures.

This shows "that B lymphocytes could play an anti-tumor role", underline in a press release Inserm, the University of Paris and the University of the Sorbonne, from which the researchers from Pr Fridman's team came.

- "More than spectators" -

These results change the perception of the role of B lymphocytes in immunotherapy, underlines Beth Helmink, surgeon oncologist at the MD Anderson Cancer Center (University of Texas) and who is co-signing a second study.

"We have shown that B lymphocytes are more than just spectactors and themselves contribute significantly to the anti-tumor immune response," she said in a statement released by her university.

This discovery is a surprise, since the abundance of B lymphocytes is sometimes seen as a sign of poor prognosis in patients with cancer.

But one of the studies shows that patients with "immunologically rich" tumors, where SLT is very present, "have shown a high response rate (50%) to immunotherapy: pembrolizumab", or Keytruda, from the laboratory American Merck.

These preliminary results (phase II clinical trial) "bring new hope for the treatment of soft tissue sarcomas", which develop in muscles, fatty tissue or even blood vessels and nerves, because they are "particularly resistant to conventional treatments "and only respond to immunotherapy in 15% of cases, emphasize Inserm, the University of Paris and the Sorbonne.

A second study by an American team made it possible to extend these observations to melanoma and kidney cancer.

This work "could be used to improve the effectiveness of cancer immunotherapy in all patients," said Lawrence Young, director of the Cancer Research Center at the University of Warwick (UK), who did not take part in studies.

Researchers do not yet know why these structures are formed in some tumors and not in others, nor what is the exact role of B lymphocytes in the success of immunotherapy: are they in the first line to produce antibodies which attack cancer cells effectively or stimulate the action of T cells?

At first, these results could help to choose which patients will be treated by immunotherapy, "thanks to a simple test allowing to identify those having immunologically rich tumors", note the French research organizations.

Ultimately, research could allow more patients to benefit from immunotherapy, "by developing a treatment that increases the formation of SLT", hopes Goran Jonsson, professor of oncology at the University of Lund (Sweden) , co-author of the third published study.

© 2020 AFP