# NATURAL CYTOTOXIC ACTIVITY & TUMORIGENESIS

> **NIH NIH R01** · UNIVERSITY OF HAWAII AT MANOA · 1988 · $138,531

## Abstract

Natural cytotoxic (NC) cells and natural killer (NK) cells belong
to a heterogeneous family of cytolytic effectors found in spleen,
lymphnodes, and peripheral blood of non-immunized individuals.
NC and NK activities have characteristics in common but are
effected by different cells, utilizing different lytic mechanisms.

It now seems likely that tumor necrosis factor (TNF) mediates NC
activity.  Experiments are proposed which will reveal whether NC
activity is mediated by secreted TNF, cell-associated TNF, or
both.

Importantly, there is substantial evidence that NC cells function
as a protective mechanism against incipient tumors.  Moreover,
there is reason to believe that NC activity functions in this role in
conjunction with an induced, antigen-specific immune response,
probably mediated by T-cells.  Accordingly, we plan experiments
to ascertain how NC activity can affect immune responses to
tumor cells, and whether TNF can affect either the induction of
an immune response, or target susceptibility to cytotoxic T-cells.

Recently we found that spleen cells elaborate a factor(s) capable
of rendering certain target cells NC resistant; a similar NC/TNF
inhibitory activity is found in normal serum.  Characterization of
this factor(s) is planned since it could aid in our understanding of
NC/TNF regulatory mechanisms, as well as prove valuable for
treatment of cancer (i.e. blocking the NC/TNF inhibitory activity
might make NC cells, or TNF, more efficient anti-cancer
modalities) or prevention of diseases thought to be mediated by
TNF (e.g., cachexia associated with cancer, or endotoxin-induced
shock resulting from Gram-negative bacterial infections).

We have also observed that certain cells which are normally
sensitive to NC lysis, become resistant to NC activity when
cultured at high density.  We have designed experiments to
ascertain whether this is a general characteristic of NC-sensitive
cells, and how high density culture affects cells such that they
become NC-resistant.  Most importantly, we will determine
whether there is a causal relationship between NC-sensitivity and
the expression of contact-inhibition, or between NC resistance
and contact-noninhibition.  Such relationships would mark a
critical prediction of anti-tumor surveillance hypotheses.

## Key facts

- **NIH application ID:** 3172633
- **Project number:** 2R01CA034805-04A2
- **Recipient organization:** UNIVERSITY OF HAWAII AT MANOA
- **SAM.gov UEI:** NSCKLFSSABF2
- **Principal Investigator:** PAUL O PATEK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $138,531
- **Award type:** 2
- **Project period:** 1988-09-01 → 1991-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172633

## Citation

> US National Institutes of Health, RePORTER application 3172633, NATURAL CYTOTOXIC ACTIVITY & TUMORIGENESIS (2R01CA034805-04A2). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3172633. Licensed CC0.

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