A report published in the journal ‘Cell’ from Cardiff University in the UK (Sewell, A., et al., Cell, 2023), describes the discovery of a “super T-cell” that attacks cancers.
Readers who follow the immune therapy literature will know that immune checkpoint inhibitors are now widely used in many cancers including lung, breast, bladder, melanoma and others.
What these investigators found is that there is a subset of immune cells (T-lymphocytes) that may be capable of eradicating, even the tiniest remnants of tumor after other immune therapies have been completed. The term TIL cell (tumor infiltrating lymphocytes) is applied to immune cells that reside inside the tumor, and these super-T-cells appears to be a subtype of TIL cell.
While the results are very interesting, they are also a bit ironic. Here in 2023, we suddenly discover that TIL cells are highly active against cancer, but it was Steven Rosenberg who first described TIL cells as “super tumor killers” in 1988 (Rosenberg, S., NEJM, December, 1988), fully 35 years ago.
Rosenberg, who I consider the father of modern cellular immune therapy, used IL2 to stimulate these cells, and continues his groundbreaking work today at the National Cancer Institute.
One must be cautious when interpreting breakthroughs in cancer research. As my TED Talk “The Future of Cancer Research Lies Behind Us” showed, the greatest breakthroughs in cancer today often reflect the re-discovery of work done years earlier by other investigators that were abandoned by a scientific community who had become so enamored with modern genomics and DNA analysis that they managed to step right over the cure.
Human metabolism is one such discipline. Another is the study of surgically removed human tissue to predict response to cancer therapy. Both are areas of interest to me, and both are fields in which I have published extensively.
Just as the Cardiff investigators re-discovered TIL cells, major institutions in the US and abroad are now touting their discovery of human tumor organoids as a “breakthrough” and their newfound model to predict cancer patient response.
What we see in cancer research, like almost any other discipline, is that things move in waves, and styles come and go.
In the early 1980s, everyone wanted to use human tissue to predict cancer outcomes. By the 1990s and early-2000s, no one wanted to use human tissue to study human cancer and now in the 2020s, everyone wants to use human cancer to predict cancer responses all over again.
Steven Rosenberg deserves credit for the observations that first identified the role of the immune system in controlling cancer and the importance of TIL cells in the process.
The question is: will today’s so-called pioneers in human tissue studies that they hope will be used for the prediction of cancer patient drug response learn from the truly groundbreaking work of European, Japanese, Canadian and US investigators who navigated the minefields to craft effective predictive platforms? Or are we doomed to see these intrepid explorers repeat the mistakes and misadventures that characterized the many failed efforts in the past? Cancer patients’ lives hang in the balance.
The human immune system is incredibly complex, which is why discoveries made in the 1980’s are still being investigated today.
Similarly, the prediction of cancer response using patient’s own tumor cells to choose drugs and combinations is extremely complex. It demands an understanding of the human tumor micro-environmental factors that shape drug-response, a field that we actually have pioneered.
While scientific breakthroughs wax and wane in popularity, cures for cancer patients are absolute. Cancer researchers must remember that for their patients, the stakes are high.
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