Impact of the COVID-19 pandemic on the diagnosis and treatment of onco-hematologic patients: a discussion paper.

We do not know the precise figure for solid organ tumors diagnosed each year in Spain and it is therefore difficult to calculate whether there has been a decrease in cancer diagnoses as a consequence of the pandemic. Some indirect data suggest that the pandemic has worsened the stage at which some non-hematological neoplasms are diagnosed. Despite the lack of robust evidence, oncology patients seem more likely to have a poor outcome when they contract COVID-19. The antibody response to infection in cancer patients will be fundamentally conditioned by the type of neoplasia present, the treatment received and the time of its administration. In patients with hematological malignancies, the incidence of infection is probably similar or lower than in the general population, due to the better protective measures adopted by the patients and their environment. The severity and mortality of COVID-19 in patients with hematologic malignancies is clearly higher than the general population. Since the immune response to vaccination in hematologic patients is generally worse than in comparable populations, alternative methods of prevention must be established in these patients, as well as actions for earlier diagnosis and treatment. Campaigns for the early diagnosis of malignant neoplasms must be urgently resumed, post-COVID manifestations should be monitored, collaboration with patient associations is indisputable and it is urgent to draw the right conclusions to improve our preparedness to fight against possible future catastrophes.

Regulation of natural killer cytotoxicity by 1,25-dihydroxyvitamin D3.

The steroid hormone 1 alpha, 25-dihydroxyvitamin D3, calcitriol, is crucial in calcium homeostasis. Calcium plays a central role in T, B, and NK cell functions, and calcitriol is a known inhibitor of T cell proliferation and immunoglobulin production. We have analyzed here the immunoregulatory effects of calcitriol on NK cell function. We show that calcitriol specifically specifically inhibits, in a time- and dose-dependent fashion, the generation of cytotoxic activity from cultured CD16+ peripheral blood NK cells. It also suppresses, at similar molar concentrations (1-10 nM), interleukin 2 (IL-2) production by PHA-activated peripheral blood lymphocytes. Calcitriol does not interfere with the cytotoxic function of NK cells, whether fresh or generated in vitro, placing the inhibition at the level of NK cell activation. Interestingly enough, exogenous IL-2 can completely reverse the suppressive effect. These findings suggest that modulation of NK cell activation by control of the internal level of IL-2 may reflect an additional paracrine calcitriol-dependent circuit with immunoregulatory consequences.

Interleukin-2 induces cytotoxic activity in lymphocytes from regional axillary nodes of breast cancer patients.

Natural killer (NK) cells and lymphokine-activated killer (LAK) cells have been involved in immunosurveillance against tumors. A normal NK activity was observed in peripheral blood (PB) mononuclear cells (MNC) from women with breast cancer, but a very low or absent NK cytotoxicity was found in the regional lymph node (RLN) MNC. However, strong cytotoxic activity against NK-resistant and NK-sensitive target cells can be induced in RLN MNC by long-term (5-day) incubation with recombinant interleukin-2 (rIL-2). This cytotoxic inducer effect of rIL-2, not observed with recombinant interferon gamma, was dose and time-dependent and was not associated with modifications in the low number of Leu 11+ or Leu 7+ cells present in the population. Both the lack of NK activity and the generation of rIL-2-activated killer cells can be readily demonstrated in either histologically affected or unaffected RLN. These results stress the value of the immunomodulators inducing cytotoxic activity in RLN MNC of patients with tumors, and are discussed in association with their possible therapeutical role.