After surgical resection of a tumor, tumor recurrence (residual microtumors) and / or remaining circulating tumor cells (CTCs) are one of the major problems in the clinic, so elucidating the involved mechanisms of recurrence and finding new therapies is essential.
Meanwhile looking at the literature, we have found a very interesting concept, platelets as cancer therapy. Platelets are the small sisters of blood cells, which don’t usually receive given much attention. They usually help to repair tissues after the resection of a tumor. Surprisingly, because of their ability to go to the surgical bed, CTCs use them, since they have the capacity to enrich the metastatic niche. If platelets were modified and conjugated with a PDL1 inhibitor (aPDL1), we would achieve a treatment directed only to the affected area where both the microtumors and the CTCs would be found, thus reducing the side effects of immunotherapy in other organs.
In the study “In situ activation of platelets with checkpoint inhibitors for post-surgical cancer immunotherapy” published in late January by Nature Biomedical Engineering, the authors precisely investigate this hypothesis and advocate for a platelet-conjugated aPDL1 (P-aPDL1) therapy . This study focused on mice that previously have had partially resected primary tumors of melanoma and triple negative breast carcinoma (leaving approximately 1% remnant), and to which different treatments were subsequently applied: resection without treatment (control), intravenous injection of aPDL1, platelets only or the conjugate of P-aPDL1. After some time, the tumors reappeared in all the previous conditions except in the mice to which the P-aPDL1 was injected, which did not present tumor recurrence. Subsequently, tumor cells were inoculated into the bloodstream of mice previously resected to mimic CTCs-driven metastasis. Unespectedly, mice treated with aPDL1 showed a significant decrease in metastasis, but not in the reappearance of the primary tumor. However, in the mice treated with P-aPDL1, platelets did a good job and not only provoke an immune response against CTCs causing their death and decreasing the spread of metastasis, but also blocked the reappearance of the primary tumor.
The treatment with PD-L1 inhibitors in patients with metastatic non-small cell lung cancer is a reality that supports immunotherapy in cancer treatments. This study shows a strategy to avoid the collateral damages of these treatments by directing them only where they are necessary.